ord" />ord" />ord" /> ord" /> TNF-? modulates genome-wide redistribution of ?Np63?/TAp73 and NF-?B c-REL interactive binding on TP53 and AP-1 motifs to promote an oncord" /><meta name="ncbi_type" content="fulltext" /><metord" /><meta name="ncbi_type" content="fullord" /><meta name="ncbi_type" content="fulltord" /><meta name="ncbi_type" content="fulltext" ord" /><meta name="ncbi_type" content="fulltext" /><meta naord" /><meta name="ncbi_type" content="fulltext" /><meta name="ncbi_objectid" content="" /><meord" /><meta name="ncbi_type" content="fulltext"ord" /><meta name="ncbi_type" content="fulltext" /ome-wide redistribution of ?Np63?/TAp73 and NF-?B c-REL interactive binding on TP53 and AP-1 motifs to promote an oncogenic gene program in squamous cancer" />ome-wide redistribution of ?Np63?/ome-wide redistribution of ?Np63?/TAp73 and NF-?B c-ome-wide redistribution of ?Np63?/TAp73 andome-wide redistribution of ?Np63?/TAp73 andome-wide redistribution of ?Np63?/TAp73 and NF-?Bome-wide redistribution of ?Np63?/TAp73 and NF-?B ome-wide redistribution of ?Np63?/TAp73 and NF-?B ome-wide redistribution of ?Np63?/TAp73 and NF-?Bome-wide redistribution of ?Np63?/TAp73 and NF-?Bome-wide redistribution of ?Np63?/TAp73 and NF-?B ome-wide redistribution of ?Np63?/TAp73 and ome-wide redistribution of ?Np63?/TAp73 and NF-?B ome-wide redistribution of ?Np63?/TAp73 andome-wide redistribution of ?Np63?/TAp73 and NF-?B ome-wide redistribution of ?Np63?/TAp73 and NF-?B c-Rome-wide redistribution of ?Np63?/TAp73 and NF-ome-wide redistribution of ?Np63?/TAp73 and NF-?B c-Rome-wide redistribution of ?Np63?/TAp73 and NF-?Bome-wide redistribution of ?Np63?/TAp73 and NF-?ome-wide redistribution of ?Np63?/TAp73 and ome-wide redistribution of ?Np63?/TAp73 and NF-?B come-wide redistribution of ?Np63?/TAp73 and NF-?B c-RELome-wide redistribution of ?Np63?/TAp73 and NF-?B c-Rome-wide redistribution of ?Np63?/TAp73 and NF-?B c-ome-wide redistribution of ?Np63?/TAp73 and NF-?B c-ome-wide redistribution of ?Np63?/TAp73 and NF-ome-wide redistribution of ?Np63?/TAp73 ome-wide redistribution of ?Np63?/TAp73 and NF-?B c-REL ome-wide redistribution of ?Np63?/TAome-wide redistribution of ?Np63?/TAp73 and NF-?B c-REL interactive binding on TP53 and AP-1 motifs to promote an oncogenic gene program in squamous cancer" /><meta name="DC.Type" content="Text" /><meta name="DC.Pome-wide redistribution of ?Np63?/TAp73 aome-wide redistribution of ?Np63?/TAp73 and NF-?B c-REL interactive binding on TP53 and AP-types (PanCancer 12) revealed frequent mutation of TP53, and amplification and expression of related TP63 isoform ?Np63 in squamous cancers. Further, aberrant expression of inflammatory ..." />types (PanCancer 12) revealed frequent mutation of TP53, and amplification and exptypes (PanCancer 12) revealed frequent mutation of TP53, antypes (PanCancer 12) revealed frequent mutation of TP53, and amplification and expression of relatetypes (PanCancer 12) revealed frequent muttypes (PanCancer 12) revealed frequent m<link rel="stylesheet" href="/content/dental/faculty/home/_jcr_content/par/external.spool?CFC__target=JY0PvIbXbtGFAX5aTGkzHtNbJoY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fcorehtml%2Fpmc%2Fcss%2F3.8%2Fpmc.min.css" type="text/css"/><link rel="stylesheet" href="/content/dental/faculty/home/_jcr_content/par/external.spool?CFC__target=CcJCwY4xr3sxHMGHR1MT4U6qc-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fcorehtml%2Fpmc%2Fcss%2F3.8%2Fpmc_extras_prnt.min.css" type="text/css" media="print"/><script type="text/javascript" src="/content/dental/faculty/home/_jcr_content/par/external.spool?CFC__target=amhVWPAmGwkxh9NF8zf47ymIUmY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fcorehtml%2Fpmc%2Fjs%2Fcommon.min.js">ty</script><script type="text/javascript" src="/content/dental/faculty/home/_jcr_content/par/external.spool?CFC__target=O3f837fAy6mmj3G4vWKLqlT7qzU-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fcorehtml%2Fpmc%2Fjs%2FNcbiTagServer.min.js">ty</script>types (PanCancer 12) revealed frequent mutation of TP53, and ampl<script type="text/javascript" src="/content/dental/faculty/home/_jcr_content/par/external.spool?CFC__target=hu8gCHBktBT60BWOCubSVjqZro-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fcorehtml%2Fpmc%2Fctxp%2Fjquery.citationexporter.js">ty</script><link rel="stylesheet" href="/content/dental/faculty/home/_jcr_content/par/external.spool?CFC__target=WCsYJbZz4OfcUKTgHyNToMjNCq8-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fcorehtml%2Fpmc%2Fctxp%2Fcitationexporter.css" type="text/css"/><script type="text/javascript" src="/content/dental/faculty/home/_jcr_content/par/external.spool?CFC__target=pcAqoS1OJ3I9v5lCvkFRhGdtgww-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fcore%2Fmathjax%2F2.6.1%2FMathJax.js%3Fconfig%3D%2Fcorehtml%2Fpmc%2Fjs%2Fmathjax-config-classic.3.4.js"></script><script type="text/javascript" src="/content/dental/faculty/home/_jcr_content/par/external.spool?CFC__target=qSPm1gzBUavaC5pRtG3tBSmlNE-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fcorehtml%2Fpmc%2Fjs%2Flarge-obj-scrollbars.min.js"></script><script type="text/javascript">types (PanCancer 12) </script>types (PanCancer 12) revealed frequent mutation of TP53, and amplification and expression of related TP63 isoform ?Np63 in squamous cancers. 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href="http://www.nature.com/authors/editorial_policies/license.html#terms">http://www.nature.com/authors/editorial_policies/license.html#terms</a></dor TNF-α broadly modulates redistribution of cREL with ΔNp63α/TAp73 complexes and signatures genome-wide in the HNSCC model UM-SCC46 using chromatin immunoprecipitation sequencing (ChIP-seq). TNF-α enhanced genome-wide co-occupancy of cREL with ΔNp63α on TP53/p63 sites, while unexpectedly promoting redistribution of TAp73 from TP53 to Activator Protein-1 (AP-1) sites. cREL, ΔNp63α, and TAp73 binding and oligomerization on NF-κB, TP53 or AP-1 specific sequences were independently validated by ChIP-qPCR, oligonucleotide-binding assays, and analytical ultracentrifugation. Function of the binding activity was confirmed using TP53, AP-1, and NF-κB specific response elements, or 3 from TP53 to Ac3 from TP533 from T3 from TP53 to Activator Protein-1 (AP-1) sites. cREL, ΔNp63α, and TAp73 binding and oligomerization on NF-κB, TP53 or AP-1 specific sequences were independently validated by ChIP-qPCR, oligonucleotide-binding assays, and analytical ultracentrifugation. Function of the binding activity was confirmed using TP53, AP-1, and NF-κB specific response elements, or <em>p21, SERPINE1</em>, and <em>IL-6</em> promoter luciferase reporter activities. Concurrently, TNF-α regulated a broad gene network with co-binding activities for cREL, ΔNp63α, and TAp73 observed upon array profiling and RT-PCR. Overlapping target gene signatures were observed in squamous cancer subsets and in inflamed skin of transgenic mice overexpressing ΔNp63α. Furthermore, multiple target genes identified in this study were linked to TP63 and TP73 activity and increased gene expression in large squamous cancer samples from PanCancer 12 T3 fr3 from3 from TP53 to Ac3 from TP53 to Activator Protein-1 (3 from TP3 from TP53 to Activator Protein-1 (AP-1) sites. cREL, ΔNp63α, 3 from 3 from3 from3 from TP53 to Activator Prote3 from TP53 to Activator Protein-1 (AP-1) sites. cREL,  fro3 from TP53 to Activator Protein-1 (AP-1) sites. cREL, ΔNp63α, and TAp73 binding and oligomerization on NF-κB, TP53 or AP-1 specific sequences were independently validated by ChIP-qPCR, oligonucleotide-binding assays, and analytical ultracentrifugation. Function of the binding activity was confirmed using TP53, AP-1, and NF-κB specific respegative HNSCC harbor genetic alterations in tumor suppressor TP53, concurrent with amplification and expression of related family member ΔNp63 in ~47% cases, and altered TNF-α-NF-κB/REL, inflammation, and death pathways in ~60% cases (<a href="#R1" rid="R1" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401336">eegative HNSCC harbor genetic alterations in tumor suppressor TP53, concurrent with amplification and expression of related family member ΔNp63 in ~47% cases, and altered <a href="#R2" rid="R2" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401335">eegative HNSCC harbor genetic alterations in tumor suppressor TP53, concurrent with amplification and expression of related family member ΔNp63 in ~47% cases, and altered TNF-α-NF-κB/REL, in<a href="#R2" rid="R2" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401311">eegative HNSCC harbor genetic alterations in tumor suppressor TP53, concurrent with amplification and expression of related family member ΔNp63 in ~47% cases, and altered TNF-α-NF-κB/REL, inflammation, and death pathways in ~60% cases (<a href="#R1" rid="R1" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401336">1</a>). In addition, the TCGA network PanCancer 12 project performed integrative analyses on 3,527 specimens of 12 cancer types, using five genome-wide high throughput platforms (<a href="#R2" rid="R2" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401335">2</a>). The project revealed a unique convergence that classified squamous cell carcinoma (SCC) oegategative HNSCC harbor genetic alterations in tumor suppressor TP53, concurrent with amplification and expression of related family member ΔNp63 in ~47% cases, and altered TNF-α-NF-κB/REL, inflammation, and death pathways in ~60% cases (<a href="#R1" rid="R1" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401336">1</a>). In addition, the TCGA network PanCancer 12 projecamaged cells (<a href="#R3" rid="R3" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401365">aamaged cells (<a href="#R3" rid="R3" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401365">3</a>). Interestingly, however, the other TP53 fam<a href="#R4" rid="R4" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401341">aamaged<a href="#R5" rid="R5" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401323">aamaged cells (<a href="#R3" rid="R3" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401365">3</a>). Interestingly, however, the other TP53 family members, TP63 and TP73, are infrequently mutated, and can potentially compensate for disrupted TP53 (<a href="#R4" rid="R4" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401341">4</a>, <a href="#R5" rid="R5" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_<a href="#R4" rid="R4" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401348">aamaged<a href="#R6" rid="R6" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401316">aamage<a href="#R8" rid="R8" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401296">aamaged cells (<a href="#R3" rid="R3" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401365">3</a>). Interestingly, however, the other TP53 family members, TP63 and TP73, are infrequently mutated, and can potentially compensate for disrupted TP53 (<a href=<a href="#R9" rid="R9" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401284">aamaged<a href="#R10" rid="R10" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401343">amamaged cells (<a href="#R3" rid="R3" class=" bibr popnereby ΔNp63α/TAp73 promote tumorigenesis and linked to inflammation in cancer are undefined.03940394;Np63α/TAp73 promote tumorigenesis and linked to inflammation in cancer are undefined.</p><p id="P5">We recently revealed that inflammatory cytokine TNF-α stimulates binding of NF-κB subunit cREL with ΔNp63 to form a protein complex 0394;Np63α/TAp0394;Np63ƊNp60394;Np<a href="#R6" rid="R6" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401342">00394;Np63α/TAp73 promote tumorigenesis and linked to inflammation in cancer are undefined.</p><p id="P5">We recently revealed that inf<a href="#R8" rid="R8" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401322">00394;Np63α/TAp73 promote tumorigenesis and linked to inflammation in cancer are undefined.</p><p id="P5">We recently revealed that<a href="#R11" rid="R11" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401276">030394;Np63α/TAp73 promote tumorigenesis and lin<a href="#R12" rid="R12" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401266">030394;Np63α/TAp73 promote tumorigenesis and linked to inflammation in cancer are undefined.</p><p id="P5">We recently revealed that inflammatory cytokine TNF-α stimulates binding of NF-κB subunit cREL with ΔNp63 to form a protein complex and displacement of TAp73 DNA binding, leading to the repression of growth arrest and apoptotic genes <em>CDKN1A (p21), NOXA</em>, and <em>PUMA</em> (<a href="#R6" rid="R6" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401342">6</a>). Complexes between cREL, RELA and ΔNp63 were also implicated in reciprocal activation of several NF-κB regulated genes (<a href="#R8" rid="R8" cl03940394;Np63α/TAp73 promote tumorigenesis and linked to inflammation in cancer are undefined.</p><p id="P5">We recently revealed that inflammatory cytokine TNF-α stimulates binding of NF-κB subunit cREL with ΔNp63 tgulatory role of cREL/ΔNp63α and TAp73 complexes. Furthermore, bioinformatic analysis of gulatory rogulatory role of cREL/ΔNp63α and TAp73 complexes. Furthermore, bioinformatic analysis of <em>in vivo</em> data from TCGA, immunohistochemistry and tissue array of HNSCC, and a ΔNp63α transgenic mouse model supports their contribution in the regulation of the cancer gene program. These findings present a new paradigm for how TNF-α and these TFs orchestrate gene programs implicated in cancer-related inflammation, survival, and migration, and help explain gulagulatogulatory role of cREL/Δgulatory role of cREL/ΔNp63α and TAp73gulatgulatory role of cREL/ΔNp63gulatory role of cREL/ΔNp63α and TAp73 complexes. Furthermore, bioinformatic analysis of <em>in vivo</em> data from TCGA, immunohistochemistry and tissue gulatgulatory role of cREL/ΔNp63α and TAp73 complexes. Furthermore, bioinformatic analysis of <em>in vivo</em> data from TCGA, immunohistochemistry and tissue array of HNSCC, and a ΔNp63α transgenic mouse model supports their contribution in the regulation of the cancer gene program. These findings present a new paradig<a href="#R6" rid="R6" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401287">ggulatory role of cREL/ΔNp63α and TAp73 complexes. Furthermore, bioinformatic analysis of <em>in vivo</em> data from TCGA, immunohisto<a href="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1" HREF="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F">gulatory role ogulatorgulatory role of cREL/ΔNp63α and TAp73 complexes. Furthermore, bioinformatic analysis of <<a href="#SD1" rid="SD1" class=" supplementary-material">gulatory rgulatory role of cREL/ΔNp63α and TAp73 complexes. Furthermore, bioinformatic analysis of <em>in vivo</em> data from TCGA, immunohistochemistry and tissue<a href="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1" HREF="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F">les/PMC5093089/les/PMCles/PM<a href="#SD12" rid="SD12" class=" supplementary-material">les/PMC5les/PMC5093089/figure/F1/" target="figure" class="fig-table-link <a href="#SD1" rid="SD1" class=" supplementary-material">les/PMC509les/PM<a href="#SD3" rid="SD3" class=" supplementary-material">leles/PMC5093089/figure/F1/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1"><span>Figure 1B</span></a>, <a href="#SD12" rid="SD12" class=" supplementary-material">Tabl<a href="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1" HREF="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F">les/PMC5093089/les/PMCles/PMC5093089/figure/F1/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1"><span>Figure 1B</span></a>, <a href="#SD12" rid="SD12" class=" supplementary-material">Table S1</a>), and similar patterns were seen on individual chromosomes (<a<a href="#SD4" rid="SD4" class=" supplementary-material">les/PMC50les/PMC5093089/figure/F1/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1<a href="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1" HREF="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F">les/PMC5093089/les/PMCles/PMC5093089/figure/F1/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1"><span>Figure 1B</span></a>, <a href="#SD12" rid="SD12" class=" supplementary-material">T<a href="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1" HREF="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F">ref="/pmc/articref="/pref="/pmc/articles/PMC5093089/figure/F1/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1"><span>Figure 1D</span></a>). The intersection sets of three TF binding peaks w<a href="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1" HREF="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F">ref="/pmc/articref="/pref="/pmc/articles/PMC5093089/figure/F1/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1"><a href="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1" HREF="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F">ref="/pmc/articref="/pref="/pmc/articles/PMC5093089/figure/F1/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1"><span>Figure 1D</span></a>). The intersection sets of three TF binding peaks <a href="#SD5" rid="SD5" class=" supplementary-material">ref="/pmcref="/pmc/articles/PMC5093089/figure/F1/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1"><span>Figure<a href="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1" HREF="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F">fig figpopup" rfig figfig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1"><span>Figure 1F</span></a>). TNF-α increased intersection binding peaks between cREL<a href="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1" HREF="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F">fig figpopup" rfig figfig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgn<a href="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1" HREF="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F">fig figpopup" rfig figfig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lg<a href="#SD11" rid="SD11" class=" supplementary-material">fig figpopup" rid-figpopfig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1"><span>Figure 1F</span></a>). TNF-α increag enriched around TSSs.g eng enriched arog enriched around TSSs.</pg enriched around TSSs.</p><!--fig ft0--><!--fig mode=article f1--><div class="fig iconbl<a class="icnblk_img figpopup" href="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F" target="figure" rid-figpopup="F1" rid-ob="ob-F1" HREF="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F"><img src="/content/dental/faculty/home/jcr:content/par/external.spool?CFC__target=ZUDDOREPLJpyHNzy7LzHUNhQs8s-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2Fnihms-753191-f0001.gif" class="small-thumb" alt="Figure 1" title="Figure 1" src-large="/pmc/articles/PMC5093089/bin/nihms-753191-f0001.jpg" SRC="/content/dental/faculty/home/jcr:content/par/external.spool?CFC__target=ZUDDOREPLJpyHNzy7LzHUNhQs8s-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2Fnihms-753191-f0001.gif" />g eng enriched around TSSs.</p><!--fig ft0-g enr<a class="figpopup" href="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F" target="figure" rid-figpopup="F1" rid-ob="ob-F1" HREF="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F">g enrichg eng enrig enriched aroundg enrg enrig enriched aroundg enriched around TSSs.</p><!--fig ft0--><!--fig mode=article f1--><div class="fig iconblock ten_col whole_rhythm clg enricheg enricg enrig enrig enrig enrig enriched around TSSs.</g enriched around TSSs.</p><!--fig ft0--><!--fig mode=article f1--><div class="fig iconblock ten_col whole_rhythm cg enrg enriched around TSSs.</p><!--fig ft0--><!--fig mode=article f1--><div class="fig iconblock ten_col whole_rhythm clearfix" id="F1" co-legend-rid="lgnd_F1"><a class="icnblk_img figpopup" hre<a href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">g enriched aroundg enricg enri<a href="#SD6" rid="SD6" class=" supplementary-material">g enricheg enriched around TSSs.</p><!--fig <a href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">g enriched aroug enricg enriched around TSSs.</p><!--fig ft0--><!--fig mode=article<a href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">g enriched aroug enricg enriched around TSSs.</p><!--fig ft0--><!--fig mode=article f1--><div class="fig iconb<a href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">ig figpopup" riig figpig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2"><span>Figure 2C</span></a>, left) and TNF-α induced TAp73 bindings (D, left) wer<a href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">ig figpopup" riig figpig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2"><span><a href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">ig figpopup" riig figpig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2"><span>Figure 2C</span></a>, left) and TNF-α induced TAp73 b<a href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">ig figpopup" riig figpig figpopup" rid<a href="#SD6" rid="SD6" class=" supplementary-material">ig figpopig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="l<a href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">ig figpopup" riig figpig figpopup" rid-figpopup="F2" s, there was abundant overlapping binding activity of basal TAp73 versus TNF-α induced p63α, ranging within ~200-300 bp (<a href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">s, there was abs, thers, there was abundant overlapping binding activity of basal TAp73 versus TNF-α induced p63α, ranging within ~200-300 bp (<a href="/pmc/art<a href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">s, there was abs, thers, there was s, ts, there was as, there was abundant overs, there was abundant overlapping binding activity of basal TAp73 versus TNF-α in<a class="icnblk_img figpopup" href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" rid-figpopup="F2" rid-ob="ob-F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F"><img src="/content/dental/faculty/home/jcr:content/par/external.spool?CFC__target=fwgySl38YbpvKCGiCiSpjx8SQ-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2Fnihms-753191-f0002.gif" class="small-thumb" alt="Figure 2" title="Figure 2" src-large="/pmc/articles/PMC5093089/bin/nihms-753191-f0002.jpg" SRC="/content/dental/faculty/home/jcr:content/par/external.spool?CFC__target=fwgySl38YbpvKCGiCiSpjx8SQ-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2Fnihms-753191-f0002.gif" />s, ts, there was abundant overlapping bindis, th<a class="figpopup" href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" rid-figpopup="F2" rid-ob="ob-F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">s, theres, ts, thes, there was abuns, ths, thes, there was abuns, there was abundant overlapping binding activity of basal TAp73 versus s, there s, thers, thes, thes, thes, thes, there was abundant oves, there was abundant overlapping binding activity of basal TAp73 versus TNF-α induced p63α, ranging wis, ths, there was abundant overlapping binding activity of basal TAp73 versus TNF-α induced p63α, ranging within ~200-300 bp (<a href="/pmc/articles/PMC5093089/figure/F2/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-<a href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">s, there was abs, thers, there was abundantracentrifugation with fluorescein-labeled DNA allowed us to measure sedimentation velocities of the protein-DNA complexes and classify their oligomerization state. Remarkably, cREL exhibited binding activities for all three REs, with a higher affinity for its own RE (<a href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">tracentrifugatitracenttracentrifugation with fluorescein-labeled DNA allowed us to measure sedimentation velocities of the protein-DNA complexes and classify their oligomeriza<a href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">tracentrifugatitracenttracentrifugation with fluorescein-labeled DNA allowed us to measure sedrmed that both cREL RHD and p73 DBD are able to bind not only to their own consensus sequences, but also to the other DNA REs, supporting the binding to motifs identified in the ChIP-seq experiment.rmedrmed trmed that both cREL RHD armed that both cREL RHD and p73 DBD are able to bind not only to their own consensus sequences, but also to thermed rmed that both cREL RHD and p73 DBD are able to bind not only to their own consensus sequences, but also to the other DNA REs, suppor<a href="#SD7" rid="SD7" class=" supplementary-material">rmed thatrmed that both cREL RHD and p73 DBD are able to bind not only to their own consensus sequences, but also to the other DNA REs, supporting the binding to motifs identified in the ChIP-seq e<a href="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F3" rid-ob="ob-F3" co-legend-rid="lgnd_F3" HREF="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F">rmed that both cRrmed thrmed t<a href="#SD13" rid="SD13" class=" supplementary-material">rmed tharmed that both cREL RHD and p73 DBD are able to bind not only to their own consensus sequences<a href="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F3" rid-ob="ob-F3" co-legend-rid="lgnd_F3" HREF="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F">rmed that both cRErmed thrmed that both cREL RHD and p73 DBD are able to bind not only to their own consen<a href="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F3" rid-ob="ob-F3" co-legend-rid="lgnd_F3" HREF="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F">rmed that both rmed thrmed that both cREL RHD and p73 DBD are able to bind not only to their own consensus sequences, but also to the other DNA REs, supporting the binding to motifs identified in the ChIP-seq experiment<a href="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F3" rid-ob="ob-F3" co-legend-rid="lgnd_F3" HREF="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F">rmed that both rmed thrmed t<a href="#SD14" rid="SD14" class=" supplementary-material"> href="# href="#SD14" rid="SD14" class=" supplementary-material">Table S3</a>). We observed a relatively stronger basal TAp73 binding activity when compared with p63α binding, consistent with the ChIP-seq and ChIP-qPCR results. Interestingly, the oligonucleotide containing a predicted AP-1 motif (p21-c) without the other motifs also exhibited TAp73 binding. These binding activities detected by ChIP-seq were validated by two different experimental methods. Thus our current study provided evidence for the co-localization of cREL, ΔNp63 and TAp73 to multiple target promoters and response elements in respo<a href="#R6" rid="R6" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401338"> href=<a href="#R8" rid="R8" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401282"> href= hre href="#SD14" href="#SD14" rid="SD14" c href="#SD14" rid="SD14" class=" supplementary-material">Table S3</a>). We observed a rel<a class="icnblk_img figpopup" href="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F" target="figure" rid-figpopup="F3" rid-ob="ob-F3" HREF="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F"><img src="/content/dental/faculty/home/jcr:content/par/external.spool?CFC__target=MiESIXehr74c8w1ODyqjqhH4I-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2Fnihms-753191-f0003.gif" class="small-thumb" alt="Figure 3" title="Figure 3" src-large="/pmc/articles/PMC5093089/bin/nihms-753191-f0003.jpg" SRC="/content/dental/faculty/home/jcr:content/par/external.spool?CFC__target=MiESIXehr74c8w1ODyqjqhH4I-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2Fnihms-753191-f0003.gif" /> hre href="#SD14" rid="SD14" class=" supple href<a class="figpopup" href="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F" target="figure" rid-figpopup="F3" rid-ob="ob-F3" HREF="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F"> href="# hre href= href="#SD14" rid href href= href="#SD14" rid href="#SD14" rid="SD14" class=" supplementary-material">Table S3</a>). We observed a href="#S href=" href= href= href= href= href="#SD14" rid="SD14" href="#SD14" rid="SD14" class=" supplementary-material">Table S3</a>). We observed a relatively st href href="#SD14" rid="SD14" class=" supplementary-material">Table S3</a>). We observed a relatively stronger basal TAp73 binding activity when compared with p63α binding, consistent with the ChIP-seq and ChIP-qPCR results. Interestingly, th<a href="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4" HREF="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F">/articles/PMC50/articl/articles/PMC5093089/figure/F4/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid<a href="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4" HREF="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F">popup" rid-figppopup" popup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4"><span>Figure 4A</span></a>, upper left). Both ΔNp63α and TAp73 also induced significant AP-1 RE inducing activity, and TNF-α further enhanced it (upper middle). cREL induced strong NF-κB reporter activity that was increased by TNF-α, while ΔNp63α and TApopup" rid-figpopopup" rid-figpopup="F4" rid-ob=popup" rid-fpopup" rid-figpopup="F4"popup" rpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4"><span>Fi<a href="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4" HREF="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F">popup" rid-figppopup" popup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lpopup" rid-figpopopup" ridpopup" rid-fpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgndpopup" rpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4"><span>Figure 4A</span></a>, upper left). Both ΔNp63α and TAp73 also induced significant AP-1 RE inducing activity, and TNF-α further enhanced it (upper middle). cRpopupopup" rid-figpopup" rid-figpopup="F4" rpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4"><span>Figure 4A</span></a<a class="icnblk_img figpopup" href="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F" target="figure" rid-figpopup="F4" rid-ob="ob-F4" HREF="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F"><img src="/content/dental/faculty/home/jcr:content/par/external.spool?CFC__target=QkKySCyG0TB46NXv1NdDhxuoqM-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2Fnihms-753191-f0004.gif" class="small-thumb" alt="Figure 4" title="Figure 4" src-large="/pmc/articles/PMC5093089/bin/nihms-753191-f0004.jpg" SRC="/content/dental/faculty/home/jcr:content/par/external.spool?CFC__target=QkKySCyG0TB46NXv1NdDhxuoqM-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2Fnihms-753191-f0004.gif" />popupopup" rid-figpopup="F4" rid-ob="ob-F4"popup<a class="figpopup" href="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F" target="figure" rid-figpopup="F4" rid-ob="ob-F4" HREF="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F">popup" rpopupopup"popup" rid-figpoppopuppopup"popup" rid-figpoppopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4"><span>Figure 4A</span></a>, upper left). Both popup" ripopup" popup"popup"popup"popup" rid-figpopup="F4" rt">We examined how TNF-α and three TFs modulated expression of 6 candidate genes identified through ChIP-seq and confirmed by microarray (<a href="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F5" rid-ob="ob-F5" co-legend-rid="lgnd_F5" HREF="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F">t">We examinedt">We et">We examined <a href="#SD7" rid="SD7" class=" supplementary-material">t">We exat">We <a href="#SD8" rid="SD8" class=" supplementary-material">t"t">We examined how TNF-α and three TFs modulated t">We examit">We examined how TNF-�<a href="#R13" rid="R13" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401362">t"t">We examined how TNF-αt">We exat">We examt">We examint">We e<a href="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4" HREF="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F">b="ob-F4" co-leb="ob-Fb="ob-F4" co-legend-rb="ob-F4"b="ob-F4" co-legend-rid="lgnd_F4"><span>Figure 4B</span></a>, uppe<a href="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4" HREF="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F">b="ob-F4" co-leb="ob-Fb="ob-F4" co-legend-rid="lgnd_F4"><span>Figb="ob-F4" b="ob-F4" b="ob-F4" co-legb="ob-F4" co-legend-rid="lgnd_F4"><span>Figure 4B</span></a>, upper panels). <em>CEBPA</em> was strongly repressed by ΔNp63α and TAp73 (<a href="/pmc/articles/PMC5093089/figure/F4/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4"><span>Figure 4B</span><b="ob="ob-F4" co-lb="ob-F4" co-legend-rid="lb="ob-F4" co-legend-rid="lgnd_F4"><span>Figure 4B</span></a>, upper panels). <em>CEBPA</e<a class="icnblk_img figpopup" href="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F" target="figure" rid-figpopup="F5" rid-ob="ob-F5" HREF="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F"><img src="/content/dental/faculty/home/jcr:content/par/external.spool?CFC__target=UxkQz4lqXImSZIgT7z2Vs8s8m7o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2Fnihms-753191-f0005.gif" class="small-thumb" alt="Figure 5" title="Figure 5" src-large="/pmc/articles/PMC5093089/bin/nihms-753191-f0005.jpg" SRC="/content/dental/faculty/home/jcr:content/par/external.spool?CFC__target=UxkQz4lqXImSZIgT7z2Vs8s8m7o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2Fnihms-753191-f0005.gif" />b="ob="ob-F4" co-legend-rid="lgnd_F4"><spanb="ob<a class="figpopup" href="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F" target="figure" rid-figpopup="F5" rid-ob="ob-F5" HREF="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F">b="ob-F4b="ob="ob-b="ob-F4" co-legeb="obb="ob-b="ob-F4" co-legeb="ob-F4" co-legend-rid="lgnd_F4"><span>Figure 4B</span></a>, upper panels). <em>CEBPA</em> was strongly reprb="ob-F4"b="ob-Fb="ob-b="ob-b="ob-b="ob-b="ob-F4" co-legend-rid="b="ob-F4" co-legend-rid="lgnd_F4"><span>Figure 4B</span></a>, upper panels). <em>CEBPA</eb="obb="ob-F4" co-legend-rid="lgnd_F4"><span>Figure 4B</span></a>, upper panels). <em>CEBPA</em> was strongly repressed by ΔNp63α and TAp73 (<a href="/pmc/articl<a href="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F5" rid-ob="ob-F5" co-legend-rid="lgnd_F5" HREF="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F">b="ob-F4" co-lb="ob-Fb="ob-F4" co-legend-rid="lgnd_F4"> ≥1.5 fold differential expression were identified during at least one time point after TNF-α treatment. Without TNF-α, a quarter of altered genes exhibited TF binding, while TNF-α significantly increased up- and down-regulated genes bound by the TFs by ~10%, together accounting for a third of differentially expressed genes (<a href="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F5" rid-ob="ob-F5" co-legend-rid="lgnd_F5" HREF="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F"> ≥1.5 fold " ≥1.5 fold differential expression were identified during at least one time point after TNF-α treatment. Without TNF-α, a quarter of altered genes exhibited TF binding, while TNF-α significantly increased up- and down-regulated genes bound by vities for the three TFs are presented for basal activities (<a href="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F5" rid-ob="ob-F5" co-legend-rid="lgnd_F5" HREF="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F">vities for the vities vities for the three TFs are presented for bas<a href="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F5" rid-ob="ob-F5" co-legend-rid="lgnd_F5" HREF="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F">vities for the vities vities for the three TFs are presented for basal activities (<a href="/pmc/articles/PMC5093089/figure/F5/" target="figure" class="fig-table-link fig figpopu<a href="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F5" rid-ob="ob-F5" co-legend-rid="lgnd_F5" HREF="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F">vities for the thrvities vities for the three TFs are presented for basal activities (<a href="/pmc/articles/PMC5093089/figure/F5/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F5" rid-ob="ob-F5" co-legend-rid="lgnd_F5"><span>Figure 5C</span></a>), or TNF-&#<a href="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F5" rid-ob="ob-F5" co-legend-rid="lgnd_F5" HREF="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F">vities for the vities vities for the three TFs are presented for basal activities (<a href="/pmc/articles/PMC5093089/figure/F5/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F5" rid-ob="ob-F<a href="#SD8" rid="SD8" class=" supplementary-material">Figure S7Figure S7</a>). Using a less stringent difference of 1.3 fold change in gene expression by TNF-α treatment, we detected 84 up-regulated genes and 61 down-regulated genes bound by all three transcription <a href="#SD15" rid="SD15" class=" supplementary-material">Figure S7Figure S7<a href="#SD16" rid="SD16" class=" supplementary-material">FiFigure S7</a>). Using a less stringent difference of 1.3 fold change in gene expression by TNF-α treatment, we detected 84 up-regulated genes and 61 down-regulated genes bound by all three transcription FiguFigureFigure S7</a>). Using a lFigure S7</a>). Using a less stringent difference of 1.3 fold change in gene expression by TNF-α treatment, we detected 84 up-regulated genes aFigurFigure S7</a>). Using a less stringent difference of 1.3 fold change in gene expression by TNF-α treatment, we detected 84 up-r<a href="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F5" rid-ob="ob-F5" co-legend-rid="lgnd_F5" HREF="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F">Figure S7</a>).Figure Figure S7</a>). Using a less stringent difference of 1.3 fold change in gene expression by TNF-α treatment, we detected 84 up-regulated<a href="#R1" rid="R1" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401292">FFigure S7</a>). Using a less stringent difference of 1.3 fold change in gene expression by TNF-α treatment, we detected 84 up-regulated genes and 61 down-regulated genes bound by all three transcripti<a href="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F6" rid-ob="ob-F6" co-legend-rid="lgnd_F6" HREF="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F">Figure S7</a>).Figure Figure S7</a>). Using a less stringent difference of 1.3 fold change in gene expression by TNF-α treatment, we detected 84 up-regulated genes and 61 down-regulated genes bound by all three transcription factors (<a href="#SD15<a href="#SD18" rid="SD18" class=" supplementary-material">Figure SFigure S7</a>). Using a less stringent difference of 1.3ges in direction of expression when comparing primary tumors to mucosa between cell line data and TCGA human tissue data. Consistent with this, an unsupervised cluster analysis and heatmap of the TCGA data for all 73 genes confirms that many of the TNFα inducible and down-regulated genes in cell lines co-cluster among 4 major tumor subsets (<a href="#SD9" rid="SD9" class=" supplementary-material">ges in diges in direction of expression when comparing primary tumors to mucosa between cell line data and TCGA human tissue data. Consistent with this, an unsupervised cluster ages in direction of expression when comparing primary tumors to mucosa beges in direction of expression when comparing primary tumors to mucosa between cell line data and TCGges in ges in dirges in direcges in direction of expression when comparing primary tumorasis, and asis, and <easis, and <em>SERPINE1</em> is also aasis, aasis, and <em>SER<a href="#R14" rid="R14" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401264">asasis,<a href="#R17" rid="R17" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401344">asasis, asisasis, and <em>asis, and <em>SERPINE1</emasis, and <em>SERPINE1</em> is also a downstream target of <em>MET</em> signaling (<a hre<a class="icnblk_img figpopup" href="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F" target="figure" rid-figpopup="F6" rid-ob="ob-F6" HREF="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F"><img src="/content/dental/faculty/home/jcr:content/par/external.spool?CFC__target=fFUmJ60pBp32hyKBEAvAXM08nJw-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2Fnihms-753191-f0006.gif" class="small-thumb" alt="Figure 6" title="Figure 6" src-large="/pmc/articles/PMC5093089/bin/nihms-753191-f0006.jpg" SRC="/content/dental/faculty/home/jcr:content/par/external.spool?CFC__target=fFUmJ60pBp32hyKBEAvAXM08nJw-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2Fnihms-753191-f0006.gif" />asisasis, and <em>SERPINE1</em> is also a dasis,<a class="figpopup" href="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F" target="figure" rid-figpopup="F6" rid-ob="ob-F6" HREF="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F">asis, anasisasis, asis, and <em>SERasis,asis, asis, and <em>SERasis, and <em>SERPINE1</em> is also a downstream target of <em>MET</em> signaling (<a href="#R14" rid="R14" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401264">1asis, andasis, aasis, asis, asis, asis, and <em>SERPINE1</em> is also a downstream target of <em>MET</em> signaling (<a href="#R14" rid="R14" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401264">14</a>-<a href="#R17" rid="R17" class=" bibr popnode tag_hotli<a href="#R8" rid="R8" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401334">aasis, and <em>SERPINE1</em> is also a downstream target o<a href="#SD8" rid="SD8" class=" supplementary-material">asis, andasis, and <em>SERPINE1<<a href="#SD11" rid="SD11" class=" supplementary-material">asis, and <em>SERPINasis, and <em>SERPINE1</em> is also a downstream target of <em>MET</em> signaling (<a href="#R14" rid="R14" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401264">14</a>-<a href="#R17" rid="R17" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401344">17</a>).</p><!--fig ft0--><!--fig mode=article f1--><div class="fig i(<a href="#R18" rid="R18" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401317">(<(<a h<a href="#R20" rid="R20" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401293">(<(<a href="#R18" rid="R18" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401317">18</a>-<a href="#R20" rid="R20" class=" bibr popnode tag_hotlink tag_tooltip" id="__t<a href="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F6" rid-ob="ob-F6" co-legend-rid="lgnd_F6" HREF="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F">(<a href="#R18"(<a hre(<a href="#R18" rid="R18" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401317">18</a>-<a href="#R20" rid="R20" class=" bibr popnode(<a href="#R18" rid="R18" class=" b(<a href="#R18" rid="R18" class=" bibr (<a href="#R18" rid="R18" class(<a href="#R18" rid="R18" class(<a href="#R18" riBB</em>). Several of these TP63 target genes also co-modulated by TNF-α co-cluster together in major subsets of TCGA HNSCC tumors <a href="#SD9" rid="SD9" class=" supplementary-material">B</em>). B</em>). SevB</em>). Several of these TP63 target genes alsB</em>)B</eB</em>). Several of these TP63 target genes also co-modulated by TNF-α co-cluster together in major subsets of TCGA HNSCC tumors (<a href="#SD9" rid="SD9" class=" supplementary-material">Figure S8</a>, e.g., <em>FOSL1, CDKN1A (p21), SERPINE1, MET, TNFAIP8</e<a href="#R21" rid="R21" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401354">B<B</em><a href="#R22" rid="R22" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401279">B<B</em>). Several of these TP63 target genes also co-modulated by TNF-α co-cluster together in major subsets of TCGA HNSCC tumors (<a href="#SD9" riB</em>). B</em>). SB</em>).B</em>). SκB pathway related genes κ;;κB pathway κκB pathway related genes <eκκB κB p;<a href="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F6" rid-ob="ob-F6" co-legend-rid="lgnd_F6" HREF="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F">κB path;�κB pathway related genes <em>Traf1</em>, <em>Ikk</em>ε and <em>Relb</em>, and their downstream genes, <em>Il-6</em>, and <em>Serpine1</em> (<a href="/pmc/anding alterations in human HNSCC tumor and tissue arrays. The nuclear-cytoplasmic distribution of cREL, ΔNp63, and TAp73 in human specimens was quantified by immunohistochemistry score. We observed increased cREL and ΔNp63, and decreased TAp73 nuclear distribution, with a reciprocal decrease in cytoplasmic cREL and increased TAp73 cytoplasmic staining in HNSCC (<a href="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F6" rid-ob="ob-F6" co-legend-rid="lgnd_F6" HREF="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F">nding alterationding anding <a href="#SD10" rid="SD10" class=" supplementary-material">ndnding alterations in human HNSCC tumor and tissue arrays. The nuclear-cytoplasmic distribution of cREL, �nding alteranding alt<a href="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1" HREF="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F">nding alterations nding anding alterations in huma<a href="#R6" rid="R6" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401308">nnding a<a href="#R8" rid="R8" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401280">nnding alterations in human HNSCC tumor and tissue arrays. The nuclear-cytoplasmic distribution of cREL, ΔNp63, and TAp73 in human specimens was quantified by immunohistochemistry score. We observed increased cREL and Δ<a href="#SD11" rid="SD11" class=" supplementary-material">nding alterations innding alterations in human HNSCC tumor and tissue arrays. Thending alnding altending altnding alterations in human HNSCC tumor and tissue arrays. The nuclear-cytoplasmic distribu<a href="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F6" rid-ob="ob-F6" co-legend-rid="lgnd_F6" HREF="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F">nding alterationding anding alterations in human HNSCC tumor and tissue arrays. The nuclear-cnding alnding altending altnding alterations in h<a href="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F3" rid-ob="ob-F3" co-legend-rid="lgnd_F3" HREF="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F">3" rid-ob="ob-F3" rid-3" ri<a href="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F5" rid-ob="ob-F5" co-legend-rid="lgnd_F5" HREF="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F">3" rid-ob="ob-F3" co-legend-rid="lgnd_F3"><span>Figures 3</span3" rid-ob="ob-F3" co-legend-rid="lgnd_F3"><span>Figures 3</span>3" rid-3" rid-3" rid-3" rid-3" rid-ob="ob-F3" co-legend-rid="lgnd_F33" rid-o3" rid-ob=3" rid-ob3" rid-ob="ob-F3" co-legend-rid="lgnd_F3"><span>Figures 3</s<a href="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F6" rid-ob="ob-F6" co-legend-rid="lgnd_F6" HREF="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F">3" rid-ob="ob-F3" rid-3" rid-ob="ob-F3" co-legend-rid="lgnd_F3"><span>Figures 3</span></a>-<a href="/pmc/articles/PMC5093089/figure/F5/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F5" rid-ob="ob-F5" co-legend-rid="lgnd_F5"><span style="position: relative;text-decoration:none;">​<span class="figpopup-sensitive-area" style="left: -0.5em;">-5).</span><3" rid-ob="ob-3" rid-ob="ob-F3" co-legend-rid="lgnd_F3"><span>Figures 3</span>3" rid-ob="o3" rid-ob=3" rid-ob="3" rid-ob="ob-3" r3" rid3" rid-ob="ob-F3" co-legen3" rid-ob="ob-F3" co-legend-rid="lgnd_F3"><span>Figures 3</span></a>-<a href="/pmc/articles/PMC5093089/figure/F5/3" ri3" rid-ob="ob-F3" co-legend-rid="lgnd_F3"><span>Figures 3</span></a>-<a href="/pmc/articles/PMC5093089/figure/F5/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F5" rid-ob="ob-F5" co-legend-rid="lgnd_F5"><span style="position: relative;text-decoration:none;">​<span class="figpopup-sensitive-area" style="left: -0.5em;">-5).</span></span><span>5</span></a>). Further, the nuclear staining of <em><a href="#R2" rid="R2" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401324">33" rid-ob="ob-F3" co-legend-rid="lgnd_F3"><span>Figures 3</span></a>-<a href="/pmc/articles/PMC5093089/figure/F5/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F5" rid-ob="ob-F5" co-legend-ridhe present study. <a href="/content/dental/faculty/home.html?CFC__target=mKlNwWgjZdWBQioFMlyby1Wlc-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF7%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F7" rid-ob="ob-F7" co-legend-rid="lgnd_F7" HREF="/content/dental/faculty/home.html?CFC__target=mKlNwWgjZdWBQioFMlyby1Wlc-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF7%2F">he present studhe preshe present study. <a href="/pmc/articles/PMC5093089/figure/F7/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F7" rid-ob="ob-F7" co-legend-rid="lgnd_F7"><span>Figure 7A</span></a> shows CircleMaps, which enable a multi-dimensional compar<a href="#R23" rid="R23" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401262">hehe pre<a href="#R24" rid="R24" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401277">hehe present study. <a href="/pmc/articles/PMC5093089/figure/F7/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F7" rid-ob="ob-F7" co-legend-rid="lgnd_F7"><span>Figure 7A</span></a> shows CircleMaps, which enable a multi-dimensional comparison of the genomic alterations, expression, and inferred pathway activities for TP53, ΔNp63, TP73, and these target genes, using the annotated PARADIGM bioinformatics analytic platform (<a href="#R23" rid="R23" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401262">23</a>, <a href="#R24" rid="R24" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401277">24</a>). The TP53 CircleMap shows that the majority of SCC tissues contain TP53 mutations (second circle), and/or copy number loss (third cirche present study. <a hrehe present study. <a href="/pmc/artihe present studhe present study. <a href="/pmche present study. <a he present study. <a href="/pmhe present study.he present study. <a href="/pmc/articles/PMC5093089/figure/F7/" target="figure" class="figs are higher across SCC tumors compared with other cancer types. By Pearson correlation analysis (<a href="/content/dental/faculty/home.html?CFC__target=mKlNwWgjZdWBQioFMlyby1Wlc-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF7%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F7" rid-ob="ob-F7" co-legend-rid="lgnd_F7" HREF="/content/dental/faculty/home.html?CFC__target=mKlNwWgjZdWBQioFMlyby1Wlc-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF7%2F">s are higher acs are hs are higher across SCC tumors compared with other cancer types. By Pearson correlation analysis (<a href="/pmc/articles/PMC5s are higher across SCC tumors s are highes are highs are higher across SCC tumors compared with other cancer types. By Pearson correlation analysis (s are higs are higher across SCC tumors compared with other ca<a href="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4" HREF="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F">s are higher acrs are hs are <a href="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F5" rid-ob="ob-F5" co-legend-rid="lgnd_F5" HREF="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F">s are higher across SCC tumors compared with other cancer typess are higher across SCC tumors compared with other cancer types. s are hs are hs are his are hs are higher across SCC tumors compared with others are hs are higher across SCC tumors compared with other cancer typess are higher acrs are higher across SCC tum<a href="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4" HREF="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F">s are higher acs are hs are hs are highers are higher across SCC tumors compared with other cancer types. By Pearson correlation analysis (<a href="/pmc/articles/PMC5093089/f<a href="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4" HREF="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F">s are higher across are hs are s ars are higher as are higher across SCC tus are higher across SCC tumors compared with other cance id="F7" co-legend-rid="lgnd_F7"><a class="icnblk_img figpopup" href="/content/dental/faculty/home.html?CFC__target=mKlNwWgjZdWBQioFMlyby1Wlc-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF7%2F" target="figure" rid-figpopup="F7" rid-ob="ob-F7" HREF="/content/dental/faculty/home.html?CFC__target=mKlNwWgjZdWBQioFMlyby1Wlc-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF7%2F"><img src="/content/dental/faculty/home/jcr:content/par/external.spool?CFC__target=fQslfF1lGoAxrcQxOCowLrkxUQ-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2Fnihms-753191-f0007.gif" class="small-thumb" alt="Figure 7" title="Figure 7" src-large="/pmc/articles/PMC5093089/bin/nihms-753191-f0007.jpg" SRC="/content/dental/faculty/home/jcr:content/par/external.spool?CFC__target=fQslfF1lGoAxrcQxOCowLrkxUQ-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2Fnihms-753191-f0007.gif" /> id= id="F7" co-legend-rid="lgnd_F7"><a cla id="<a class="figpopup" href="/content/dental/faculty/home.html?CFC__target=mKlNwWgjZdWBQioFMlyby1Wlc-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF7%2F" target="figure" rid-figpopup="F7" rid-ob="ob-F7" HREF="/content/dental/faculty/home.html?CFC__target=mKlNwWgjZdWBQioFMlyby1Wlc-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF7%2F"> id="F7" id= id="F id="F7" co-legen id=" id="F id="F7" co-legen id="F7" co-legend-rid="lgnd_F7"><a class="icnblk_img figpopup" href="/pmc/articles id="F7" id="F7 id="F id="F id="F id="F id="F7" co-legend-rid="lgnd_F7"><a id="F7" co-legend-rid="lgnd_F7"><a class="icnblk_img figpopup" href="/pmc/articles/PMC5093089/figure/F id=" id="F7" co-legend-rid="lgnd_F7"><a class="icnblk_img figpopup" href="/pmc/articles/PMC5093089/figure/F7/" target="figure" rid-figpopup="F7" rid-ob="ob-F7"><img src="/pmc/articles/PMC5093089/<a href="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F3" rid-ob="ob-F3" co-legend-rid="lgnd_F3" HREF="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F"> id="F7" co-leg id="F7 id="<a href="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F5" rid-ob="ob-F5" co-legend-rid="lgnd_F5" HREF="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F"> id="F7" co-legend-rid="lgnd_F7"><a class="icnblk_img figpopup" id="F7" co-legend-rid="lgnd_F7"><a class="icnblk_img figpopup" id="F7 id="F7 id="F7 id="F7 id="F7<a href="#R6" rid="R6" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401331"> id="F<a href="#R8" rid="R8" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401329"> id="F<a href="#R25" rid="R25" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401314"> i id="F7" co-legend-rid="lgnd_F7"><a class="icnblk_img figpopup" href="/pmc/articles/PMC5093089/figure/F7/" target="figure" rid-figpopup="F7" rid-ob="ob-F7"><img src="/pmc/art<a href="#R2" rid="R2" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401346">=="__tag_569401346">2</a>). However, the network(s) linking TP63 and NF-κB family members and target genes has not been well elucidated. We thus searched within the interconnected network of differentially activated PARADIGM pathways, linked through regulatory hubs with >15 downstream targets, derived from a larger interconnected network displaying differentially aferred between the C2-Squamous-like subtype and other tumors, as detailed in <a href="#SD11" rid="SD11" class=" supplementary-material">ferred between the Cferred<a href="#SD17" rid="SD17" class=" supplementary-material">ferred bferred<a href="#SD2" rid="SD2" class=" supplementary-material">ferred betferred<a href="#R26" rid="R26" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401345">feferred between the C2-Squamous-like subtype and other tumors, as detailed in <a href="#SD11" rid="SD11" class=" supplementary-material">Supplemental Methods</a>, <a href="#SD17" rid="SD17" class=" supplementary-<a href="/content/dental/faculty/home.html?CFC__target=mKlNwWgjZdWBQioFMlyby1Wlc-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF7%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F7" rid-ob="ob-F7" co-legend-rid="lgnd_F7" HREF="/content/dental/faculty/home.html?CFC__target=mKlNwWgjZdWBQioFMlyby1Wlc-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF7%2F">ferred between ferred ferred between the C2-Squamous-like subtype and other tumors, as detailed in <a href="#SD11" rid="SD11" class=" supplementary-material">Supplemental Methods</a>, <a href="#SD17" rid="SD17" class=" supplementary-material">Table S5</a>, <a href="#SD2" rid="SD2" class=" supplemenferred betweferred betferred betwferred <a href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">ferred betweenferred ferre<a href="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F6" rid-ob="ob-F6" co-legend-rid="lgnd_F6" HREF="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F">ferred between the C2-Squamous-like subtype and other tumors, aferred between the C2-Squamous-like subtype and other tumors, asferred ferred ferred ferred ferred between the C2-Squamous-like subtype and other tumors, as detailed in <a href="#SD11" rid="SD11" class=" supplementary-material">ferred between the C2-Squamous-like subtype and otheferred between the C2-Squamous-like subtype and other tferred between thferred between the C2-Squamous-like subtype and other tumors, as detailed in <a href="#SD11" rid="SD11" class=" supplementary-material">Supplemental Methods</a>, <a href="#SD17" rid="SD17" cecting ΔNp63α, TP53 and AP-1 transcription complexes (among other regulatory hubs), links a larger number of target genes identified in this study by existing experimental data (<a href="#SD2" rid="SD2" class=" supplementary-material">ecting ìting ΔNp63α, TP53 and AP-1 transcription complexes (among other regulatory hubs), links a <a href="#SD2" rid="SD2" class=" supplementary-material">ecting Ϭting ΔNp63α, TP53 and AP-1 transcription complexes (among other regulatory hubs), links a larger number of target genes identified in this study by existing experimental data (<a href="#SD2" rid="SD2" class=" supplementary-mate<a href="#SD17" rid="SD17" class=" supplementary-material">ecting &ectinectiectingectingecting ΔNp63α, ecting ΔNp63α, TP53 and AP-1 transcriptionectinecting ΔNp63α, TP53 and AP-1 transcription complexes (among other regulatory hubs), links a larger number of target genes identified in this study by existing experimental data (<a href="#SD2" rid="SD2" class=" supplementary-material">Figure S10A</a>). Although not all target genes identified from our current study are linked by this expanded network (<a href="#SD2" rid="SD2" class=" supplementary-material">Figure S10A-B</a>), they are significantly enriched among the 4213 differentiall<a href="/content/dental/faculty/home.html?CFC__target=P7zEFevgnf5HglbD0vrxxXxNlzk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF8%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F8" rid-ob="ob-F8" co-legend-rid="lgnd_F8" HREF="/content/dental/faculty/home.html?CFC__target=P7zEFevgnf5HglbD0vrxxXxNlzk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF8%2F">ecting 㧬ting ecting ΔNp63α, TP53 and AP-1 transcription complexes (among other regulatory hubs), links a larger number of target genes identified in this study by existing experimental data (<a href="#SD2" rid="SD2" class=" supplementary-material">Figure S10A</a>). Although not all target genes identified<a href="#R1" rid="R1" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401310">eecting<a href="#R2" rid="R2" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401330">e</a>). Furthermore, our current data are consistent with previous mechanistic studies demonstrating how TNF-α induced changes alter the DNA binding of c-REL, ΔNp63 and TAp73 family members (<a href="#R6" rid="R6" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401347"> tag_h<a href="#R8" rid="R8" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401313"> tag_hotlink tag_tooltip" id="__tag_569401347">6</a>, <a href="#R8" rid="R8" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401313">8</a>). Our studies showed that these transcription factors regulate genes involved in several aspects of cell fate including cell proliferation, stemness, survival/apoptosis, and mi<a href="#R27" rid="R27" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401275"> t tag_h<a href="#R28" rid="R28" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401299"> t tag_h tag tag_hotlink t tag_hotlink tag_tooltip" tag_hotlink tag_tooltip" id="__tag_569401347">6</a>, <a href="#R8" rid="R8" class=" bibr<a class="icnblk_img figpopup" href="/content/dental/faculty/home.html?CFC__target=P7zEFevgnf5HglbD0vrxxXxNlzk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF8%2F" target="figure" rid-figpopup="F8" rid-ob="ob-F8" HREF="/content/dental/faculty/home.html?CFC__target=P7zEFevgnf5HglbD0vrxxXxNlzk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF8%2F"><img src="/content/dental/faculty/home/jcr:content/par/external.spool?CFC__target=3svnSZd9Ig3JaCuUFjDvZZ5vE-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2Fnihms-753191-f0008.gif" class="small-thumb" alt="Figure 8" title="Figure 8" src-large="/pmc/articles/PMC5093089/bin/nihms-753191-f0008.jpg" SRC="/content/dental/faculty/home/jcr:content/par/external.spool?CFC__target=3svnSZd9Ig3JaCuUFjDvZZ5vE-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2Fnihms-753191-f0008.gif" /> tag tag_hotlink tag_tooltip" id="__tag_569 tag_<a class="figpopup" href="/content/dental/faculty/home.html?CFC__target=P7zEFevgnf5HglbD0vrxxXxNlzk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF8%2F" target="figure" rid-figpopup="F8" rid-ob="ob-F8" HREF="/content/dental/faculty/home.html?CFC__target=P7zEFevgnf5HglbD0vrxxXxNlzk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF8%2F"> tag_hot tag tag_h tag_hotlink tag_ tag_ tag_h tag_hotlink tag_ tag_hotlink tag_tooltip" id="__tag_569401347">6</a>, <a href="#R8"ulation of cREL, ΔNp63α and TAp73 chromatin occupancy and reprogramming of TAp73 from TP53 to AP-1 sites to promote inflammatory and cancer gene programsulation oulationulatioulatioulatioulation of cREL, ΔNp63α and TAp73 chromatin occupancy and reprogramming of TAp73 from TP53 to AP-1 sites to promote inflammatory and cancer gene programs</strong></span></div></div></div><p id="P21">After cross comparison of 12 diff<a href="#R2" rid="R2" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401286">uulation of cREL, ΔNp63α and TAp73 chromatin occupancy and reprogramming of TAp73 from TP53 to AP-1 sites to promote inflammatory and cancer gene programs</strong></span></div></div></div><p id="P21">After cross comparison of 12 different cancer types, TCGA PanCancer 12 project uncovered several unique signatures that differentiate squamous cancers from other cancer types, s<a href="#R23" rid="R23" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401285">ululatioulatulation of cREL, ΔNp63α and TAp73 chromatin occupancy and reprogramming of TAp73 from TP53 to AP-1 sites to promote inflammatory and cancer gene programs</strong></span></div></div></div><p id="P21"><a href="#R6" rid="R6" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401349">uulatio<a href="#R8" rid="R8" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401352">uulation of cREL, ΔNp63α and TAp73 chromatin occupancy and reprogramming of TAp73 from TP53 to AP-1 sites to promote inflammatory and cancer gene programs</strong></span></div></div></div><p id="P21">After cross comparison of 12 different cancer types, TCGA PanCancer 12 project uncovered several unique signatures t<a href="#R6" rid="R6" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401363">uulation of cREL, ΔNp63α and TAp73 chromatin occupancy and reprogramming of TAp73 from TP53 to AP-1 sites to promote inflammatory and cancer gene programs</strong></span>on of target genes of TP53 as well as AP-1 and REL/NF-κB. Such TP63/TP73 compensatory TP53 function has been associated with higher sensitivity to cisplatin chemotherapy in both HNSCC (<a href="#R29" rid="R29" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401357">onon of <a href="#R30" rid="R30" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401270">onon of target genes of TP53 as well as AP-1 and REL/NF-�<a href="#R31" rid="R31" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401315">onon of target genes of TP53 as well as AP-1 and REL/NF-κB. Such TP63/TP73 compensatory TP53 function has been associated with higher sensitivity to con oon of target genes of TP53 as well as AP-1 and REL/NF-κB. Such TP63/TP73 compensatory TP53 function h<a href="#R1" rid="R1" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401297">oon of target genes of TP53 as well as AP-1 and REL/NF-κB<a href="#R6" rid="R6" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401289">oon of target genes of TP53 as well as AP-1 and REL/NF-κB. Such TP63/TP73 compensatory TP53 function has been associated with higher sensitivity to cisplatin chemotherapy in both HNSCC (<a href="#R29" rid="R29" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401357">on of target genes of on of taron of taon of target genes of TP53 as well as AP-1 and REL/NF-κB. Such TP63/TP73 compensatory TP53 function has been associated with higher sensitivity to cisplatin chemotherapy in both HNSCC (<a href="#R29" rid="R29" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401357">29</a>, <a href="#R30" rid="R30"<a href="#R6" rid="R6" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401294">oon of target genes of TP53 as well as AP-1 and REL/NF-κB. Such TP63/TP73 compensatory TP53 function has been associated with higher sensitivity to cisplatin chemotherapy in both HNSCC (<a href="#R29" rid="R29" class=" bibr popnode tag_hotlink tag_tooltipfamily members (<a href="#R32" rid="R32" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401306">fafamily<a href="#R33" rid="R33" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401272">fafamilyfamifamily members (<a href="#R32" rid="R32" class=" bibr popnode tag_hotlparent function of TP63/TP73 in compensating for TP53 and promoting oncogene expression. First, such compensatory activity is associated with enhanced expression of typical TP53 target genes, such as parent function parent funparent funcparent function of TP63/TP73 in c<a href="#R9" rid="R9" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401319">pparent<a href="#R30" rid="R30" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401290">paparent function of TP63/TP73 in compensatin<a href="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F3" rid-ob="ob-F3" co-legend-rid="lgnd_F3" HREF="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F">parent functioparent paren<a href="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F5" rid-ob="ob-F5" co-legend-rid="lgnd_F5" HREF="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F">parent function of TP63/TP73 in compensating for TP53 and promoparent function of TP63/TP73 in compensating for TP53 and promotparent parent parent parent parent function of TP63/TP73 in compensating for TP5<a href="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F6" rid-ob="ob-F6" co-legend-rid="lgnd_F6" HREF="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F">parent functionparent parent function of TP63/TP73 in compen<a href="/content/dental/faculty/home.html?CFC__target=mKlNwWgjZdWBQioFMlyby1Wlc-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF7%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F7" rid-ob="ob-F7" co-legend-rid="lgnd_F7" HREF="/content/dental/faculty/home.html?CFC__target=mKlNwWgjZdWBQioFMlyby1Wlc-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF7%2F">parent functioparent parent function of TP63/TP73 in compensating for TP53 and promoting oncogene expression. First, such compensatory activity is associated with enhanced expression of typical TP53 target genes, such<a href="#R6" rid="R6" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401356">pparent<a href="#R8" rid="R8" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401360">pparent function of TP63/TP73 in compensating for TP53 and promoting oncogene expression. First, such compensatory activity is associated with enhanced expression of typarent fuparent f<a href="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4" HREF="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F">4/" target="fi4/" tar4/" t<a href="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F6" rid-ob="ob-F6" co-legend-rid="lgnd_F6" HREF="/content/dental/faculty/home.html?CFC__target=K1JMsRrEEJBbesRROMKDIHQQ0M-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF6%2F">4/" target="figure" class="fig-table-link fig figpopup" rid-fig4/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="4/" tar4/" tar4/" tar4/" tar4/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4"><span>Figure 4</span></a>-<a href="/pmc/articles/PMC5093089/figure/F6/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F6" r<a href="#R2" rid="R2" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401318">44/" target="figure" class="fig-table-link fig ogenic activity of ΔNp63α in squamous cancers, including promoting tumor cell proliferation, migration, colony formation, and inflammatory responses (<a href="#R8" rid="R8" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401326">oogenic activity of ΔNp63α in squamous cancers, including promoting tumor cell proliferation, migration, colony formation, and inflammatory responses (<a href="#R8" rid="R8" class=" bibr popnode tag_hotlink tag_tool<a href="#R2" rid="R2" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401302">oogenic activity of ΔNp63α in squamous cancers, including promoting tumor cell proliferation, migration, colony formation, and inflammatory responses (<a href="#R8" rid="R8" class=" bibr popnode ta<a href="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F1" rid-ob="ob-F1" co-legend-rid="lgnd_F1" HREF="/content/dental/faculty/home.html?CFC__target=gD2ox2FFtYxvoQLnB5NVWgSjEY-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF1%2F">ob="ob-F1" co-ob="ob-ob="o<a href="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4" HREF="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F">ob="ob-F1" co-legend-rid="lgnd_F1"><span>Figure 1</span></a>-<aob="ob-F1" co-legend-rid="lgnd_F1"><span>Figure 1</span></a>-<aob="ob-ob="ob-ob="ob-ob="ob-ob="ob-F1" co-legend-rid="lgnd_F1"><span>Figure 1</span></a>-<a href="/pmc/articles/PMC5093089/figure/F4/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4"><span style="position: relative;text-decoration:none;">​<span <a href="/content/dental/faculty/home.html?CFC__target=mKlNwWgjZdWBQioFMlyby1Wlc-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF7%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F7" rid-ob="ob-F7" co-legend-rid="lgnd_F7" HREF="/content/dental/faculty/home.html?CFC__target=mKlNwWgjZdWBQioFMlyby1Wlc-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF7%2F">ob="ob-F1" co-lob="ob-ob="ob-F1<a href="#SD2" rid="SD2" class=" supplementary-material">ob="ob-F1"ob="obob="ob="ob-F1" co-legend-rid="lgnd_F1"><span>Figure 1</span></a>-<a href="/pmc/articles/PMC5093089/figure/F4/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4"><span style="position: relative;text-decoration:none;">​<span class="figpopup-sensitive-area" style="left: -0.5em;">-4)</span></span><span>4</span></a>) in this study. This novel finding is also supported by the PanCancer 12 data indicating that inflammatory gene signatures linked by cytokine TNF-α and <a href="#R34" rid="R34" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401269">obob="ob-F1" co-legend-rid="lgnd_F1"><span>Figure 1</span></a>-<a href="/pmc/articles/PMC5093089/figure/F4/" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgn<a href="#R35" rid="R35" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401281">obob="ob-F1" co-legend-rid="lgnd_F1"><span>Figure 1</span></a>-<a href="/pmc/articles/PMC<a href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">="F2" rid-ob="="F2" r="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2"><span>Figure 2</span></a>), which are similar to the sequences of TP53/TP63/<a href="#R34" rid="R34" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401304">="="F2"<a href="#R39" rid="R39" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401273">="="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2"><span>Figure 2</span></a>), which are similar to the sequences of TP53/TP63/TP73 and nearby AP-1 binding motifs observed in previous studies (<a href="#R34" rid="R34" class=" bibr popno<a href="#R6" rid="R6" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401359">=="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2"><span>Figure 2</span></a>), which <a href="#R9" rid="R9" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401325">=="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2"><span>Figure 2</span></a>), which are similar to the sequences of TP53/TP63/TP73 and nearby AP-1 binding motifs observed in previous studies (<a href="#R34" rid="R34" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569<a href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">="F2" rid-ob="ob-F2" ="F2" r="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2"><span>Figure 2</span></a>), which are similar to the sequences of TP53/TP63/TP73 and nearby AP-1 binding motifs observed in previous studies (<a href="#R34" rid="R34" class=" bib="F2="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2"><span>Figure 2</span></a>), which are similar to the sequences of TP53/TP63/TP73 and nearby AP-1 binding motifs observed in previous studies (<a href="#R34" rid="R34" class=" bibr popnode ta<a href="#R6" rid="R6" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401283">=="F2" <a href="#R8" rid="R8" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401353">=="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2"><span>Figure 2</span></a>), dually bind the same minimal TP53RE, or if TP73 can bind to AP-1 REs independent of ΔNp63α or other cofactors. Our sedimentation velocity centrifugation experiments revealed that both cREL and TP73 bind these DNA REs and can form dimers and/or tetramers upon DNA binding. These results provide biophysical support to the model of co-localized binding of cREL and TP73 suggested by the ChIP-seq and bioinformatics analyses. Collectively, the different experimental approaches provide mechanistic details of how TFs can occupy binding sites at the same as well as very close promoter sequences.dualdually bind the same minimal TP53RE, or if TP73 can bind to AP-1 REs independent of ΔNp63α or other cofactors. Our sedimentation velocity centrifugation experiments revealed that both cREL and TP73 bind thes<a href="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F4" rid-ob="ob-F4" co-legend-rid="lgnd_F4" HREF="/content/dental/faculty/home.html?CFC__target=0m8QfWyaHZf4HCp2GtcV7c3rtpg-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF4%2F">dually bind thedually dually bind the same minimal TP53RE, or if TP73 can bind to AP-1 REs independent of ΔNp63α or other cofactors. Our sdually bind the dually bind the same minimal TP53dually bdually bind the same minimal TP53RE, or if TP73 can bind to AP-1 REs independent of ΔNp63α or other cofactors. Our sedimentation velocity centrifugation <a href="#R8" rid="R8" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401288">ddually<a href="#R40" rid="R40" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401263">dudually bind the same minimal TP53RE, or if TP73 can bidually bind the dually bindually bind dually bind the same minimal TP53RE, or if TP73 can bind to AP-1 REs independent of <a href="#R9" rid="R9" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401358">ddually<a href="#R31" rid="R31" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401267">dudually<a href="#R35" rid="R35" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401340">dudually<a href="#R41" rid="R41" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401259"> r rid="<a href="#R42" rid="R42" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401339"> r rid="R41" class=" bibr popnode tag_hotlink tag_tooltip" id<a href="#R43" rid="R43" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401265"> r rid="<a href="#R44" rid="R44" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401332"> r rid="R41" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401259">41</a>, <a href="#R42" rid="R42" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401339">42</a>), as well as induced specific AP-1 promoter activity (<a href="#R43" rid="R43" class=" b rid rid="R41" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401259">41</a>, <a href="#R42" rid="R42" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569<a href="#R45" rid="R45" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401364">tatag_to<a href="#R46" rid="R46" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401355">tatag_tooltip" id="__tag_569401364">45</a>, <a href="#R46" rid="R46" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401355">46</a>), the latter through MEK/ERK signaling. These findings <a href="#R2" rid="R2" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401268">ttag_tooltip" id="__tag_569401364">45</a>, <a href="#R46" rid="R46" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401355">46</a>), the latter through MEK/ERK signaling. These findings aretag_tooltip" itag_tooltip" id="__tag_569401364">45</a>, <a href="#R4tag_toolttag_tooltitag_tooltag_tooltip" id="__tag_569401364">45</a>, <a href="#R46" rid="R46" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401355">46</a>), the latter through MEK/ERK signaling. These findings are also consistent with the Pan-TCGA data, where the Squamous-like cancer type exhibited elevated activity of MAPK signaling pathways (<a href="#R2" rid="R2" <a href="#R47" rid="R47" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401333">popopnod<a href="#R48" rid="R48" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401305">popopnode tag_hotlink tag_tooltip" id="__tag_569401333">47</a>, <a href="#R48" rid="R48" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401305">48</<a href="#R35" rid="R35" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401301">popopnod<a href="#R43" rid="R43" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401328">popopnod<a href="#R44" rid="R44" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401261">popopnode tag_hotlink tag_tooltip" id="__tag_569401333">47</a>, <a href="#R48" rid="R48" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401305">48</a>). Our data are supported by others’ observations that p73 and AP-1 family members can enhance each other's binding and transcription popnpopnode tag_hotlink tag_tooltip" id="__tag_569401333">47</a>, <a href="#R48" rid="R48" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401305">48</a>). Our data are supported by others’ observations that p73 and AP-1 family members can enhance each other's binding and tr<a href="#R6" rid="R6" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401327">ppopnod<a href="#R8" rid="R8" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401312">ppopnod<a href="#R31" rid="R31" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401295">popopnode tag_hotlink tag_tooltip" id="__tag_569401333">47</a>, <a href="#R48" rid="R48" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_5<a href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">popnode tag_hotlink tagpopnodepopnod<a href="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F3" rid-ob="ob-F3" co-legend-rid="lgnd_F3" HREF="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F">popnode tag_hotlink tag_tooltip" id="__tag_569401333">47</a>, <<span class="figpopup-sensitive-area" style="left: -0.5em;">,3C).an clasan clasan classan clasan class="figpopup-sensitive-area" style="left: -0.5em;">,3C).</span></span><span>3C</span></a>). Thirdly, nuclear TAp73 binding is displaced from TP53/p63 <a href="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F2" rid-ob="ob-F2" co-legend-rid="lgnd_F2" HREF="/content/dental/faculty/home.html?CFC__target=SPdgmTkFQc6zfwIuriLPkcHq0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF2%2F">an class="figpan clasan cla<a href="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F3" rid-ob="ob-F3" co-legend-rid="lgnd_F3" HREF="/content/dental/faculty/home.html?CFC__target=USOSumtIx3G74OSv5lTn5zc6o-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF3%2F">an class="figpopup-sensitive-area" style="left: -0.5em;">,3C).<an class="figpopup-sensitive-area" style="left: -0.5em;">,3C).an clasan clasan clasan clasan clas<a href="#R6" rid="R6" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401307">aan class="figpopup-sensitive-area" style="left: -0.5em;">,3C).</span></span><span>3C</span></a>). Thirdly, nuclear TAp73 bindin<a href="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F" target="figure" class="fig-table-link fig figpopup" rid-figpopup="F5" rid-ob="ob-F5" co-legend-rid="lgnd_F5" HREF="/content/dental/faculty/home.html?CFC__target=XsF4dITER4QcbxbXC6zDGgdDXyk-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Ffigure%2FF5%2F">an class="figpan clasan class="figpopup-sensitive-area" sty<a href="#R33" rid="R33" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401278">anan cla<a href="#R43" rid="R43" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401298">anan class="figpopup-sensitive-area" style="left: -0.5em;">,3C).</span></span><span>3C</span></a>). Thirdly, nuclear<a href="#R49" rid="R49" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401366">anan class="figpopup-sensitive-area" style="left: -0.5em;">,3C).</span></span><span<a href="#R34" rid="R34" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401321">anan claan can class="figpopup-sensitive-area" style="left: -0.5em;">,3C).</span></<a href="#R6" rid="R6" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401320">aan cla<a href="#R8" rid="R8" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401271">aan cla<a href="#R48" rid="R48" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401361">R4R48" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401361">48</a>) reveal a complex, genome-wide transcriptional regulatory mechanism whereby TP53, NF-κB and AP-1 family members interact to promote a broad signaling network favoring tumor survival and inflammation. Our current study helps explain the global mechanisms underlying the newly discovered deregulated TP53/p63<a href="#R2" rid="R2" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401337">RR48" class=" bibr popnode tag_hotlink<a href="#R50" rid="R50" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401274">R4R48" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401361">48</a>) reveal a complex, genome-wide transcriptional regulatory mechanism whereby TP53, NF-κB and AP-1 family members interact to promote a broad signaling network favoring tumor survival and inflammation. OuR48"R48" cR48" class=" bibr popnode tag_hR48" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_56940136R48" R48" class=" bibr popnode tag_hotlink tagR48" class=" bibr popnode tag_hotlink tag_tooltip"R48" R48" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401361">48</a>) reveal a complex, genome-wide transcriptional regulatory mechanism whereby TP53, NF-κB and AP-1 family members interact to promote a broad signaling network favoring tumor survival and inflammation. Our current study helps explain the global mechanisms underlying the newly discovered deregulated TP53/p63 network and inflammation, presented recently by TCGA pan-cancer project (<a href="#R2" rid="R2" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569<a href="#R51" rid="R51" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401351">R4R48" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401361">48</a>) reveal a complex, genome-wide transcriptional regulatory mechanism whereby TP53, NF-κB and AP-1 family members interact to promotein-DNA binding sites when analyzing ChIP-seq data. This method is specifically designed to detect the promoter transcription factor binding sites, which are typically located within a few hundred DNA base pairs. In our study, the default setting was selected, which is commonly utilized and suitable to our datasets. Detected peak regions were visualized mainly by using the CisGenome browser (<a href="#R52" rid="R52" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401350">tetein-DNA binding sites when analyzing ChIP-seq data. This method is specifically designed to detect the promoter transcription factor binding sites, which are typically located within a few hundred DNA base pair<a href="#R53" rid="R53" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401260"> p popnode tag_hotlink tag_tooltip" id="__tag_569401260">53</a>). A binomial test was used in this method <a href="#R54" rid="R54" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401309"> p popnode tag_hotlink ta popnode ta popnode tag_hotlink tag_tooltip" id="__tag_569401260">53</a>). A <a href="#R55" rid="R55" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401291"> p popnode tag_hotlink tag_tooltip" id="__tag_569401260">53</a>). A binomial test was used in this method to obtain the p value of each comparison. Gibbs Sampler (<a href="#R54" rid="R54" class=" bibr popnode tag_hotlink tag_tooltip" id="__tag_569401309">54</a>) was used for the <em>de novo</em> motif search for binding site sequences and MEME-ChIP suit (<a href="#R55" rid="R55" class=" bi<a href="#SD12" rid="SD12" class=" supplementary-material"> popnode tag_hotlink popnode tag_hotlink tag_tooltip" id="__tag_569401260">53</a>). A binomial test was used in this method to obtain the p value of each comparison. 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HREF="/content/dental/faculty/home.html?CFC__target=SrsgA6vubBB6zMjjyGjkLrnfws-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2FNIHMS753191-supplement-Supplemental_Figure_6.tif">ere to view.</a><suere ere to view.</a>ere toere toere toere to view.</a><sup>(439K, xlsx)<ere to view.</a><sup>(439ere tere to view.</a><sup>(439K, xlsx)</sup></div></<a href="/content/dental/faculty/home.html?CFC__target=Ctwt5jEbEK5KXkOe4bYkI1TIG0I-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2FNIHMS753191-supplement-Supplemental_Figure_7.tif" HREF="/content/dental/faculty/home.html?CFC__target=Ctwt5jEbEK5KXkOe4bYkI1TIG0I-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC5093089%2Fbin%2FNIHMS753191-supplement-Supplemental_Figure_7.tif">ere to ere to view.ere ere to view.</a>ere toere toere toere to view.</a><sup>(366K, tif)</ere to view.</a><sup>(366ere tere to view.</a><sup>(366K, tif)</sup></div></d<a 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href="/pmc/articles/PMC5093089/bin/NIHMS753191-supplement-Supplemental_Figure_8.tif">Click here to view.</a><sup>(15M, tif)</sup></div></div><div class="sec suppmat" id="SD10"><h4>Supplemental Figure 9</h4><div class="sup-box half_rhythm" id="d37e1428"><a href="/pmc/articles/PMC5093089/bin/NIHMS753191-supplement-Supplemental_Figure_9.tif">Click here to view.</a><sup>(5.8M, tif)</sup></div></div><div class="sec suppmat" id="SD2"><h4>Supplemental Figure 10</h4><div class="sup-box half_rhythm" id="d37e1432"><a href="/pmc/articles/PMC5093089/bin/NIHMS753191-supplement-Supplemental_Figure_10.tif">Click here to view.</a><sup>(1.6M, tif)</sup></div></div></div><div id="S15" class="tsec sec"><h2 class="head no_bottom_margin" id="S15title">Acknowledgments</h2><div class="sec"><p id="__p1">The authors thank Dr. Fan Yang (NCI/NIH), Dr. Kairong Cui (NHLBI/NIH), Dr. Bingmei Zhu (NIDDK/NIH), Mr.ere ere to view.</a><sup>(366K, tif)</sup></div>d ZC are supported by intramural projects ZIA-DC-000073, ZIA-DC-000074, and RAR and SS are supported by a grant from NIH (R01AR049238). JMS acknowledges support from NCI (R01-CA180778 and U24-CA143858), Stand Up to Cancer, Prostate Cancer Foundation, and the Movember Foundation.d ZCd ZC ad ZC ad ZC are supported by intramural projects ZIA-DC-000073,d ZC are supported by intramural projects ZIA-DC-000073, ZIA-DC-000074, and RAR and ZC d ZC are supported bd ZC are supported by intramural projed ZC are supported by intrad ZC are supporss="p p-first">Supplemental informationss="ss="p p-first">Supplemental information</p><p id="P33" class="p p-last">For information on cell lines, reagents and antibodies, chromatin immunoprecipitation (ChIP) analyses, quantitative PCR and RT-PCR, plasmid and siRNA transfection, reporter gene assays, oligo-based binding assays, protein expression and purification, Analytical ultracentrifugation, microarray data collection and analysis, immunohistochemistry, the ΔNp63α transgenic mouse model, CircleMap, and PARADIGM SuperPathway subnetwork, sequence data storage, see the Supplemental Mass="ss="ss="p ss="p ss="p p-first">Supplemental information</p><p id="P33" css="p p-first">Supplemental information</p><p id="P33" class="p p-last">For informass="pss="p p-first">Supplemental information</p><p id="ss="p p-first">Supplemental information</p><p idss="p p-first">Supplemental information</p><p id="P33" class="p p-last">For information on cell lines, reagents and antibodies, chromatiss="p ss="p p-first">Supplemental informss="p p-firsss="p p-first">Supplementss="p p-first">Suppless="p p-ss="p p-first">Supplemental in<a class="int-reflink" href="/content/dental/faculty/home.html?CFC__target=GlVCb2DoRyRgsEuWgcAH8p8Eo0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC4311405%2F" HREF="/content/dental/faculty/home.html?CFC__target=GlVCb2DoRyRgsEuWgcAH8p8Eo0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC4311405%2F">ss="p p-first">Sss="pss="p p-fss="p p-first">Supplemental infor<a href="/content/dental/faculty/home.html?CFC__target=pfM9xVrp5c2rFHqVnOPbkjkLR0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F25631445" target="pmc_ext" ref="reftype=pubmed&article-id=5093089&issue-id=278503&journal-id=319&FROM=Article%7CCitationRef&TO=Entrez%7CPubMed%7CRecord&rendering-type=normal" HREF="/content/dental/faculty/home.html?CFC__target=pfM9xVrp5c2rFHqVnOPbkjkLR0-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F25631445">ss="p ss="pss="p pss="p pss="p <div class="ref-cit-blk half_rhythm" id="R2">2. div class="ref-cit-blk half_rhythm" id="R2">2. <span class="element-citation">Hoadley KA, Yau C, Wolf DM, Cherniack AD, Tamborero D, Ng S, et al. 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familyfamily member isoform DeltaNp63alpha by the nucleafamily member isoform DeltaNp63alpha by the nuclear factor-kappaB targeting kinase IkappaB kinase beta. <span><span class="ref-journal">Cancer Res. </span>2010;<span class="ref-vol">70</span>(4):1419?29.</familyfamily member isoform DeltaNp63alpha by tfamily membefamily member isoform Delfamily member isofofamily mfamily member isoform DeltaNp6<a class="int-reflink" href="/content/dental/faculty/home.html?CFC__target=qUBZp24X5QyGEPXqmjnu3IiwTI-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1849987%2F" HREF="/content/dental/faculty/home.html?CFC__target=qUBZp24X5QyGEPXqmjnu3IiwTI-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1849987%2F">family member isfamilfamily mefamily member isoform DeltaNp63al<a href="/content/dental/faculty/home.html?CFC__target=zQONeEpsvDIWW1nMDYzxvUDGI-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F17446929" target="pmc_ext" 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HREF="/content/dental/faculty/home.html?CFC__target=6nwNWh1zh2iTvjwIhKtEkANUks-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F15849742">d=319&d=319d=319&ad=319&ad=319&d=319&FROM=Article%7CCitationRef&TO=Entrezd=319&FROM=Article%7CCitationRef&TO=Entrez%7CPubMed%7CRecord&rendering-type=normal">PubMed</a>]</span></span></div><div class="ref-cit-blk half_rhythm" id="R41">41d=319&d=319&FROM=Article%7CCitationRef&d=319&FRd=319&FROM=Article%d=319&FROM=Artid=319&d=319&FROM=Article%7CCitation<a href="/content/dental/faculty/home.html?CFC__target=xTiK2d5tR9yAyOfNqvclr8M5zc-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F17496887" target="pmc_ext" ref="reftype=pubmed&article-id=5093089&issue-id=278503&journal-id=319&FROM=Article%7CCitationRef&TO=Entrez%7CPubMed%7CRecord&rendering-type=normal" HREF="/content/dental/faculty/home.html?CFC__target=xTiK2d5tR9yAyOfNqvclr8M5zc-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F17496887">d=319&d=319d=319&ad=319&ad=319&d=319&FROM=Article%7CCitationRef&TO=Entrezd=319&FROM=Article%7CCion">Toh WH, Siddique MM, Boominathan L, Lin KW, Sabapathy K. c-Jun regulates the stability and activity of the p53 homologue, p73. ion">Tion">Toh WH, Siddique MM, Boominathan Lion">Toh WH,ion">Toh WH, Siddique MM,ion">Toh WH, Siddiqueion">Toh ion">Toh WH, Siddique MM, Boomina<a href="/content/dental/faculty/home.html?CFC__target=IqZfYzcWHxIjCKr8CwYR6EKH5c-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F15302867" target="pmc_ext" ref="reftype=pubmed&article-id=5093089&issue-id=278503&journal-id=319&FROM=Article%7CCitationRef&TO=Entrez%7CPubMed%7CRecord&rendering-type=normal" HREF="/content/dental/faculty/home.html?CFC__target=IqZfYzcWHxIjCKr8CwYR6EKH5c-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F15302867">ion">Tion">ion">Toion">Toion">Tion">Toh WH, Siddique MM, Boominathan L, Lin KW, Sion">Toh WH, Siddique MM, Boominathan L, Lin KW, Sabapathy K. c-Jun regulates the stability and activity of the p53 homologue, p73. <span><span class="ref-journal">J Biol Chem. </span>2004;<span class="ref-vol">279</span>(43):44713?22.</span> <span class="nowraion">Tion">Toh WH, Siddique MM, Boominathan L, Liion">Toh WH,ion">Toh WH, Siddique Mion">Toh WH, Siddiion">Toh ion">Toh WH, Siddique MM, Boomina<a href="/content/dental/faculty/home.html?CFC__target=N7uwLvRh0DkmyVRIhLVY7st494A-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F11234901" target="pmc_ext" ref="reftype=pubmed&article-id=5093089&issue-id=278503&journal-id=319&FROM=Article%7CCitationRef&TO=Entrez%7CPubMed%7CRecord&rendering-type=normal" HREF="/content/dental/faculty/home.html?CFC__target=N7uwLvRh0DkmyVRIhLVY7st494A-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F11234901">ion">Tion">ion">Toion">Toion">Tion">Toh WH, Siddique MM, Boominathan L, Lin KW, Sion">Toh WH, Siddique MM, Boominathan L, Lin KW, Sabapathy K. c-Jun regulates the stability and ion">Tion">Toh WH, Siddique MM, Boominathan L, ion">Toh WH,ion">Toh WH, Siddique Mion">Toh WH, Siddiion">Toh ion">Toh WH, Siddique MM, Boomina<a href="/content/dental/faculty/home.html?CFC__target=brPYGWFRO7ZKv0Wl1FGmB0TC9jQ-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F11988758" target="pmc_ext" ref="reftype=pubmed&article-id=5093089&issue-id=278503&journal-id=319&FROM=Article%7CCitationRef&TO=Entrez%7CPubMed%7CRecord&rendering-type=normal" HREF="/content/dental/faculty/home.html?CFC__target=brPYGWFRO7ZKv0Wl1FGmB0TC9jQ-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F11988758">ion">Tion">ion">Toion">Toion">Tion">Tohss="ref-cit-blk half_rhythm" id="R47">47. ss="ref-cit-blk half_rhythm" id="R47">47. <span class="element-citation">Ondrey FG, Dong G, Sunwoo J, Chen Z, Wolf JS, Crowl-Bancroft CV, et al. Constitutive activation of transcription factors NF-(kappa)B, AP-1, and NF-IL6 in human head and neck squamous cell carcinoma cell lines that express pro-iss="ress="ref-cit-blk half_rhythm" id="R47">47ss="ref-cit-ss="ref-cit-blk half_rhyss="ref-cit-blk hass="ref-css="ref-cit-blk half_rhythm" id="<a href="/content/dental/faculty/home.html?CFC__target=AxPgIHjTJgLTabECWBOustgU-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F10506755" target="pmc_ext" ref="reftype=pubmed&article-id=5093089&issue-id=278503&journal-id=319&FROM=Article%7CCitationRef&TO=Entrez%7CPubMed%7CRecord&rendering-type=normal" HREF="/content/dental/faculty/home.html?CFC__target=AxPgIHjTJgLTabECWBOustgU-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F10506755">ss="ress="rss="refss="refss="ress="ref-cit-blk half_rhythm" id="R47">47. <span clss="ref-cit-blk half_rhythm" id="R47">47. <span class="element-citation">Ondrey FG, Dong G, Sunwoo J, Chen Z, Wolf JS, Crowl-Bancroft CV, et al. Constitutive activation of transcription factors NF-(kappa)B, AP-1, and NF-IL6 in human head and necss="ress="ref-cit-blk half_rhythm" id="R47ss="ref-cit-ss="ref-cit-blk half_rhyss="ref-cit-blk halss="ref-ss="ref-cit-blk half_rhythm" i<a class="int-reflink" href="/content/dental/faculty/home.html?CFC__target=QFCoBFRBasmhgWxMuVIbpVh0C4-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3926900%2F" HREF="/content/dental/faculty/home.html?CFC__target=QFCoBFRBasmhgWxMuVIbpVh0C4-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC3926900%2F">ss="ref-cit-blk ss="rss="ref-css="ref-cit-blk half_rhythm" id="<a href="/content/dental/faculty/home.html?CFC__target=WAcPMAsRPMk5rjAtjUO7Jjxno-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F23455325" target="pmc_ext" ref="reftype=pubmed&article-id=5093089&issue-id=278503&journal-id=319&FROM=Article%7CCitationRef&TO=Entrez%7CPubMed%7CRecord&rendering-type=normal" HREF="/content/dental/faculty/home.html?CFC__target=WAcPMAsRPMk5rjAtjUO7Jjxno-https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F23455325">ss="ress="rss="refss="refss="ress="ref-cit-blk half_rhythm" id="R47">47. <span clss="ref-cit-blk half_rhythm" id="R47">47. <span class="element-citation">Ondrey FG, Dong G, Sunwoo J, Chen Z, Wolf JS, Crowl-Bancroft CV, et al. 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