TP63 (tumor protein p63)

2012-12-01   Austin Mattox , Zhong Chen , Carter Van Waes 

Clinical Genomics Unit, Tumor Biology Section, Head, Neck Surgery Branch, National Institute on Deafness, Other Communication Disorders, NIH, Bethesda, MD, 20892, USA





Human TP63 was first isolated from human total genomic DNA by screening with an 800 bp PCR fragment obtained from probing with primers designed to anneal to regions in contiguous exons of p53 and p73, including the intervening introns (Yang et al., 1998). The resulting clones recovered from SK-N-MC neuroepithelioma total genomic DNA encoded proteins with two different N termini (TA and ΔN) and five different C termini (α, β, γ, δ, and ε; figure 1) (Yang et al., 1998; Mangiulli et al., 2009). Short splicing isoforms lacking exon 4 have been observed in invasive breast carcinomas (de Biase et al., 2010) that are not presented in figure 1.


The TP63 gene spans 267 kb, contains 16 exons, encodes 680 amino acids for the longest isoform, and has 12 isoforms formed by alternative promoter usage and alternative splicing (Augustin et al., 1998; Muzny et al., 2006; Parsons et al., 2009; Vanbokhoven et al., 2011). The six variants with TA and ΔN at the N-terminal and α, β, γ at the C-terminal are the most known and studied isoforms.


Atlas Image
Figure 1. The Human TP63 isoforms. A) Human TAp63 and ΔNp63 with α, β, γ, δ, ε splice variant protein isoforms are shown. TP63 protein functional domains are depicted. TA: transactivation domain; ΔN: N-terminally truncated isoform; DBD: DNA binding domain; OD: oligomerization domain; the second TA domain; SAM: sterile alpha motif; ID: inhibitory domain. B) Exon schema and corresponding domains of the human TP63 gene. Alternative promoter use produces TA (transactivation) and N-terminally truncated (ΔN) isoforms, and alternative splicing produces C-terminal variants. Alternatively spliced forms of exon 10 are designated as 10* and 10**.


Human TP63 encodes the p63 protein, of which the longest isoform contains 680 amino acids, has molecular weights ranging from 44 to 77 kDa, depending on specific alternative promoter usage and alternative splicing (Augustin et al., 1998; Yang et al., 1998). TP63 comprises up to five types of domains, depending on the isoform, and may contain transactivation (TA), DNA Binding (DBD), oligomerization (OD), C-terminal sterile alpha motif (SAM), and/or C-terminal transcription inhibitory (ID) domains (Moll and Slade, 2004). The N-terminus may consist of a TA domain or a truncated version (ΔN) lacking the acidic TA domain that is derived from an alternative promoter and initiation codon in intron 3 (Yang et al., 1998). The 3 end of both TAp63 and ΔNp63 may be alternatively spliced to yield isoforms α, β, γ, and δ, while the ε-isoform is formed from transcriptional termination in exon 10 (Mangiulli et al., 2009). TAp63α and ΔNp63α contain a protein-protein interaction SAM domain and a trans-inhibitory domain, resulting from the masking of N-terminal TA domain residues. The δ- and ε-isoform proteins are formed by transcriptional termination in the second TA domain and after the OD, respectively (Mangiulli et al., 2009) (figure 1).

TP63 binds DNA as either a homo- or a heterotetramer, with isoform composition of the tetramer possibly determining transactivation activity. p63 may also form mixed dimers or tetramers with p73 at relatively higher affinity than with p53, suggesting functional cross talk to regulate transcriptional activity (Davison et al., 1999; Natan and Joerger, 2012). p63 appears to form a dimer of dimers, with monomers consisting of a β-strand followed by two helices (H1 and H2) that adopt a z-shaped double-hairpin conformation with little intramolecular contact between structural elements (Natan and Joerger, 2012). Monomers dimerize via intermolecular antiparallel β-sheet interactions and antiparallel packing of the H1 helices, with important hydrophobic contacts made by key leucine, valine, tyrosine, methionine, and isoleucine residues (Natan and Joerger, 2012). Tetramers are formed by hydrophobic H1-H1 interactions and H2-mediated contact where the H2 helices from the primary dimer clasps the adjacent dimer, packing the tetramer in an orthogonal fashion via H1 helices arrangement (Natan and Joerger, 2012). Analysis of the DBD of TP63 shows higher similarity to that of p73 than p53, and appears to bind a 10-bp DNA sequence containing a "CATG" motif with A/T-rich flanking regions (Chen et al., 2011).


TP63 expression is found in fetal and adult tissues, including the skin, cervix, vaginal epithelium, urothelium, prostate, heart, testis, kidney, thymus, brain, and spleen (Yang et al., 1998). Immunohistochemistry of p63 often shows strong nuclear-localized staining in basal epithelial cells. Additionally, TA and ΔN isoforms appear to be differentially expressed in particular tissue types. TAp63 variants are prevalent in the heart, testis, kidney, thymus, brain, and cerebellum. ΔNp63 transcripts are detected heavily in epithelial cells, kidney, spleen, and thymus, but not in the heart, liver, testis, or brain (Yang et al., 1998; Dötsch et al., 2010).


As a transcription factor, p63 is normally present in the nucleus (Yang et al., 1998).


TP63 acts as a motif-specific transcriptional activator or repressor, depending on the presence of TA or ID domains in the specific p63 isoform (Yang et al., 1998). It plays a critical role in the maintenance of progenitor-cell populations that encourage epithelial development and morphogenesis (Romano et al., 2009). ΔNp63, once thought to serve as a dominant negative regulator due to its lack of a full TA domain, has recently been implicated in transcriptionally activating and repressing target genes such as Keratin 5 and Keratin 14 to dictate early epithelial development and determine keratinocyte cell fate and lineage choices (Yang et al., 1998; Romano et al., 2009). Less is known about TAp63 function. Mice with germline deletion of TAp63 display blisters, decreased hair morphogenesis, and potential maintenance of adult stem cells, though full characterization of TAp63 function is lacking (Su et al., 2009).
While the interactomes of TP53 and TP73 have been systematically analyzed and cataloged, until recently, no such information had been compiled for TP63 (Tozluoglu et al., 2008; Collavin et al., 2010). Recent protein chip analysis has elucidated 144 proteins that specifically interact with TP63 and are implicated in cell growth/death/survival, chromatin remodeling and gene regulation, RNA processing, protein trafficking and degradation, and other and epithelial differentiation (Huang et al., 2012). A representative protein and its function from each of the aforementioned categories are described below, while a complete list may be found in the supplemental data of Huang et al. (2012).
Cell growth/survival: Signal Transducer and Activator of Transcription 3 (STAT3) - STAT3 is a latent cytoplasmic transcription factor activated in response to various interleukins and growth factors that binds the promoter regions of IL-6-induced plasma protein and intermediate-early genes (Akira et al., 1994; McLoughlin et al., 2005; Huang et al., 2012).
Chromatin remodeling: SWI/SNF Regulator of Chromatin 1 (SMARCC1) - SMARCC1 is a component of the larger SWI/SNF complex responsible for chromatin remodeling necessary for transcriptional activation of certain genes (Wang et al., 1996; Ring et al., 1998; Huang et al., 2012).
Gene regulation/expression: Eukaryotic Translation Initiation Factor 4A2 (EIF4A2) - EIF4A2 plays an important role in the binding of mRNA to the 43S pre-initiation complex during the beginning of protein synthesis (Sudo et al., 1995; Huang et al., 2012).
RNA processing: Splicing Factor 3b, Subunit 4 (SF3B4) - SF3B4 interacts with other spliceosome proteins to help cross-link a 29-nucleotide region in the pre-mRNA near the branch-point sequence in the A complex (Champion-Arnaud and Reed, 1994; Huang et al., 2012).
Protein trafficking: Trafficking Protein Particle Complex 2-Like (TRAPPC2L) - TRAPPC2L is part of the TRAPP multi-subunit tethering complex involved in intracellular vesicle trafficking (Scrivens et al., 2011; Huang et al., 2012).
Protein degradation: Ubiquitin Conjugation Factor E4 B Isoform 1 (UFD2A) - UFD2A has been shown to promote monoubiquitination of p53 and, in combination with MDM2, to promote p53 polyubiquitination (Wu and Leng, 2011; Wu et al., 2011; Huang et al., 2012).
Epithelial differentiation: Keratin 1 (KRT1) - KRT1 is a marker for terminal differentiation in the mammalian epidermis (Lessin et al., 1988; Huang et al., 2012).
Through protein-protein interactions with other transcription and cofactors, TP63 also contributes to the transcriptional regulation of genes involved in cellular differentiation, proliferation/survival, growth suppression, apoptosis, adhesion, inflammation, and metabolism (Perez and Pietenpol, 2007; Viganò and Mantovani, 2007; Yang et al., 2011). Recent work by our laboratory has identified protein-protein interactions between ΔNp63α, TAp73, and c-REL that function to regulate key genes involved in growth arrest and apoptosis of mutant p53 head and neck squamous cell carcinoma (HNSCC) (Lu et al., 2011). Functionally important genes representing each of the aforementioned categories are described below, while more comprehensive reviews may be found in Perez and Pietenpol (2007) and Viganò and Mantovani (2007).
Cellular differentiation: Jagged 1 (JAG1) - JAG1 is the ligand of the Notch receptor. Its binding causes a proteolytic cleavage cascade, leading to translocation of the intracellular component of the Notch receptor and subsequent activation of transcription factors with key roles in cell differentiation and morphogenesis (Gray et al., 1999; Sasaki et al., 2002; Guarnaccia et al., 2004). Overexpression of p63γ has been shown to dramatically upregulate JAG1 protein levels in colorectal cancer, osteogenic sarcoma, lung cancer, hepatocellular carcinoma, and glioma (Sasaki et al., 2002).
Proliferation/survival: Epidermal Growth Factor Receptor (EGFR) - EGFR is the receptor for epidermal growth factor and is involved in modulating cellular functions such as cell proliferation, differentiation, and survival by activating various intracellular signaling cascades such as RAS and STAT that transcribe target genes important in cellular proliferation and survival (Carpenter, 1984; Jamnongjit et al., 2005; Testoni et al., 2006). Knockdown of ΔNp63α has been shown to reduce expression of EGFR in keratinocytes (Testoni et al., 2006).
Growth suppression: Cyclin-Dependent Kinase Inhibitor 1A (CDKN1A) - CDKN1A (p21) associates with cyclins A, D, and E to prevent the G1-S phase transition in mammals (el-Deiry et al., 1993; Westfall et al., 2003). Overexpression of ΔNp63α has been shown to reduce expression of p21 in HEK cells (Westfall et al., 2003).
Apoptosis: p53-Upregulated Modulator of Apoptosis (PUMA) - PUMA binds to BCL2 to induce rapid and profound apoptosis by cytochrome c release (Yu et al., 2001; Flores et al., 2002). Additionally, recent work has shown that a complex of ΔNp63α, with TAp73 or c-REL, can modify expression of key growth arrest and apoptotic genes such as p21WAF1, NOXA, and PUMA (Lu et al., 2011; Yang et al., 2011).
Adhesion: Integrin Alpha 6 (ITGA6) - ITGA6 is a cell surface adhesion molecule that may help regulate migration and layer formation, especially in epithelial cells. Mouse models deficient in ITGA6 display severe blistering of the skin and other epithelia and die shortly after birth (Georges-Labouesse et al., 1996; Carroll et al., 2006). Loss of endogenous p63 in mammary epithelial cells has been shown to induce detachment and cell death, presumably because p63 regulates expression of key adhesion molecules such as ITGA6, ITGB1, ITGB4 other ECM components, and cadherins-catenins (Carroll et al., 2006; Yang et al., 2011).
Inflammation: ΔNp63 overexpression has been observed in head and neck squamous cell carcinoma (HNSCC), which are associated with inflammation. TNF-α, a potent pro-inflammatory cytokine, promoted NF-κB, c-REL and RELA complexes with nuclear ΔNp63, to promote a broad-spectrum production of cytokines and chemokines (Lu et al., 2011; Yang et al., 2011). In addition, in squamous epithelia of ΔNp63α transgenic mice, severe inflammation, skin lesions and erythema were observed after ΔNp63 expression was induced. Microscopically, hyperplastic and hyperproliferative epidermis with diffuse infiltration of inflammatory cells in the dermis was observed (Yang et al., 2011). NF-κB family proteins, c-Rel and RelA, and numerous inflammatory cytokines and chemokines were significantly upregulated in ΔNp63 transgenic mice.
Metabolism: Fatty Acid Synthase (FASN) - FASN catalyzes the conversion of Acetyl-CoA and Malonyl-CoA into long-chain saturated fatty acids with the help of NADPH (Wakil, 1989; DErchia et al., 2006). ΔNp63α (and TAp73α) expression has also been shown to induce promoter and enhancer activity in human FASN gene by binding to p53 response elements (DErchia et al., 2006).
Mouse models TP63 knockout mice are born alive but have striking developmental defects including absent or truncated limbs, lack of stratified epithelia, and lack hair follicles, teeth, and mammary glands. Thus, TP63 is essential for epidermal-mesenchymal interactions during embryonic development, including regenerative limb proliferation, craniofacial and epithelial development, and differentiation of squamous epithelia (Yang et al., 1998; Mills et al., 1999; McKeon, 2004; Laurikkala et al., 2006). Recently, ΔNp63α transgenic mice have been developed using tissue-specific tetracycline inducible expression. Mice expressing ΔNp63α under a tissue-specific promoter (SPC) for lung epithelium exhibited Keratin 5 and 14 induction, trans-differentiation to an epidermal cell lineage, and squamous metaplasia. Overexpression of ΔNp63α under a K5 promoter in wild-type epidermis results in severe defects in hair follicle development and cycling, leading to severe hair loss and a depleted hair follicle stem-cell niche (Romano et al., 2009; Romano et al., 2010). In addition, ΔNp63α overexpression induced marked skin inflammation, and skin hyperplasia (Yang et al., 2011). A more detailed summary of the phenotypes of different p63 knockout and transgenic mouse models has recently been published (Vanbokhoven et al., 2011).


In addition to humans, the TP63 gene is conserved in chimpanzees, dogs, cows, mice, rats, chicken, and zebrafish, and evolutionary precursors have been detected in Cnidarians.

Implicated in

Entity name
Various cancers
Genome-wide association studies and in vivo work have identified TP63 mutations and/or overexpression in multiple cancers, including lung, bladder, esophageal, and head and neck squamous cell carcinoma (Rocco et al., 2006; Rothman et al., 2010; Hu et al., 2011; Stransky et al., 2011; Yang et al., 2011; Ellinghaus et al., 2012). While these studies have correlated certain mutations with an increased risk for cancer, the molecular effects of these mutations are not as well characterized as those in the aforementioned autosomal dominant disorders. Immunohistochemistry (IHC) in head and neck squamous cell carcinoma (HNSCC) has identified overexpression of TP63 isoforms in the majority of tumor specimens. Although the tumorigenic effect of all the TP63 isoforms has yet to be fully understood, unregulated TP63 expression is an early pathogenic event in HNSCC and inhibition of TP63 can induce apoptotic cell death (Westfall and Pietenpol, 2004; Chen et al., 2005; Rocco et al., 2006). Additionally, ΔNp63α has been shown to increase the half-life of hypoxia-inducible factor 1α, leading to upregulation of vascular endothelial growth factor (VEGF) expression in vitro in human non-small cell carcinoma cell lines (Senoo et al., 2002). Transcriptional activation of matrix metalloproteases (MMPs) has also been seen with high levels of ΔNp63α (Patturajan et al., 2002; Hildesheim et al., 2004). TAp73/ΔNp63α interaction has also been shown to mediate chemosensitivity to cisplatin in primary breast cancers (Leong et al., 2007). More recently, ΔNp63 overexpression is shown in HNSCC to correlate with increased epithelial inflammation, proliferation, and migration by regulating gene programs important in cancer progression (Yang et al., 2011). In addition, TNF-α, a potent pro-inflammatory cytokine, promoted c-REL translocation and complexes with nuclear ΔNp63, while TAp73 dissociated from ΔNp63 and the promoters of key growth arrest and apoptosis genes p21CIP1/WAF1, NOXA, and PUMA. Increased nuclear ΔNp63α was detected in human HNSCC tumors, and hyperplastic squamous epithelia of transgenic mice overexpressing ΔNp63α (Lu et al., 2011). Such a novel mechanism explains how inflammation activates proto-oncogenic NF-κB and overcomes TP53/p63/p73 family mediated tumor suppression. Furthermore, it has been found that ΔNp63α interacts with IκB kinases, and IKKβ promotes ubiquitin-mediated proteasomal degradation of ΔNp63α. Conversely, IKKβ inhibition attenuated cytokine- or chemotherapy-induced degradation of ΔNp63α (Chatterjee et al., 2010).
Entity name
Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome
ADULT syndrome may be caused by heterozygous mutations in the TP63 gene, including missense mutations R298Q and R227Q. Features include ectrodactyly, syndactyly, finger and toenail dysplasia, hypoplastic breasts and nipples, freckling, lacrimal duct atresia, frontal alopecia, primary hypodontia, and loss of permanent teeth (Reisler et al., 2006; Rinne et al., 2006).
Entity name
Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3)
EEC3 is an autosomal dominant disorder caused by a heterozygous mutation in TP63, most likely in the DNA-binding domain. Clinically, EEC3 presents with absence of the central parts of the hands and feet, resulting in split-hand/foot malformations, ectodermal dysplasia, and cleft lip that may or may not include cleft palate (Maas et al., 1996; Akahoshi et al., 2003).
Entity name
Hay-Wells syndrome
While similar to phenotype to ADULT syndrome and EEC3, Hay-Wells syndrome is caused by a heterozygous mutation in TP63 in the sterile alpha motif (SAM) domain. Hay-Wells Syndrome is characterized by congenital ectodermal dysplasia with course, sparse hair, dystrophic nails, scalp infections, hypodontia, maxillary hypoplasia, and cleft lip/palate (Hay and Wells, 1976; McGrath et al., 2001).
Entity name
Limb-mammary syndrome (LMS)
LMS is caused by a heterozygous mutation in the TP63 gene and is allelic to ADULT syndrome. Features of LMS include severe hand/food anomalies and hypoplasia/aplasia of the mammary gland and nipples (Propping and Zerres, 1993; van Bokhoven et al., 2001).


Pubmed IDLast YearTitleAuthors
128385572003EEC syndrome type 3 with a heterozygous germline mutation in the P63 gene and B cell lymphoma.Akahoshi K et al
75124511994Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway.Akira S et al
97998411998Cloning and chromosomal mapping of the human p53-related KET gene to chromosome 3q27 and its murine homolog Ket to mouse chromosome 16.Augustin M et al
63270621984Properties of the receptor for epidermal growth factor.Carpenter G et al
167150762006p63 regulates an adhesion programme and cell survival in epithelial cells.Carroll DK et al
79588711994The prespliceosome components SAP 49 and SAP 145 interact in a complex implicated in tethering U2 snRNP to the branch site.Champion-Arnaud P et al
214642852011Structures of p63 DNA binding domain in complexes with half-site and with spacer-containing full response elements.Chen C et al
157522592005Expression of p63 protein and mRNA in oral epithelial dysplasia.Chen YK et al
203791962010p53-family proteins and their regulators: hubs and spokes in tumor suppression.Collavin L et al
165826252006The fatty acid synthase gene is a conserved p53 family target from worm to human.D'Erchia AM et al
103734841999p73 and p63 are homotetramers capable of weak heterotypic interactions with each other but not with p53.Davison TS et al
204843882010p63 and p73, the ancestors of p53.Dötsch V et al
220764642012Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia.Ellinghaus E et al
119327502002p63 and p73 are required for p53-dependent apoptosis in response to DNA damage.Flores ER et al
86731411996Absence of integrin alpha 6 leads to epidermolysis bullosa and neonatal death in mice.Georges-Labouesse E et al
100792561999Human ligands of the Notch receptor.Gray GE et al
153585572004Exon 6 of human Jagged-1 encodes an autonomously folding unit.Guarnaccia C et al
9464101976The syndrome of ankyloblepharon, ectodermal defects and cleft lip and palate: an autosomal dominant condition.Hay RJ et al
146474292004Gadd45a regulates matrix metalloproteinases by suppressing DeltaNp63alpha and beta-catenin via p38 MAP kinase and APC complex activation.Hildesheim J et al
217253082011A genome-wide association study identifies two new lung cancer susceptibility loci at 13q12.12 and 22q12.2 in Han Chinese.Hu Z et al
226729052012Global tumor protein p53/p63 interactome: making a case for cisplatin chemoresistance.Huang Y et al
162607202005Epidermal growth factor receptor signaling is required for normal ovarian steroidogenesis and oocyte maturation.Jamnongjit M et al
165249292006p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation.Laurikkala J et al
174469292007The p63/p73 network mediates chemosensitivity to cisplatin in a biologically defined subset of primary breast cancers.Leong CO et al
24614201988Chromosomal mapping of human keratin genes: evidence of non-linkage.Lessin SR et al
219338822011TNF-α promotes c-REL/ΔNp63α interaction and TAp73 dissociation from key genes that mediate growth arrest and apoptosis in head and neck cancer.Lu H et al
87376551996EEC syndrome and genitourinary anomalies: an update.Maas SM et al
197007722009Identification and functional characterization of two new transcriptional variants of the human p63 gene.Mangiulli M et al
111599402001Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of p63.McGrath JA et al
150375442004p63 and the epithelial stem cell: more than status quo?McKeon F et al
159760282005IL-6 trans-signaling via STAT3 directs T cell infiltration in acute inflammation.McLoughlin RM et al
102272931999p63 is a p53 homologue required for limb and epidermal morphogenesis.Mills AA et al
152804452004p63 and p73: roles in development and tumor formation.Moll UM et al
166419972006The DNA sequence, annotation and analysis of human chromosome 3.Muzny DM et al
221003062012Structure and kinetic stability of the p63 tetramerization domain.Natan E et al
191429592009Comprehensive mutational analysis and mRNA isoform quantification of TP63 in normal and neoplastic human prostate cells.Parsons JK et al
120868512002DeltaNp63 induces beta-catenin nuclear accumulation and signaling.Patturajan M et al
172973082007Transcriptional programs regulated by p63 in normal epithelium and tumors.Perez CA et al
84568381993ADULT-syndrome: an autosomal-dominant disorder with pigment anomalies, ectrodactyly, nail dysplasia, and hypodontia.Propping P et al
170419312006Further phenotypic and genetic variation in ADULT syndrome.Reisler TT et al
96930441998Five SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin (SMARC) genes are dispersed in the human genome.Ring HZ et al
167240072006Delineation of the ADULT syndrome phenotype due to arginine 298 mutations of the p63 gene.Rinne T et al
164134712006p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis.Rocco JW et al
194619982009An active role of the DeltaN isoform of p63 in regulating basal keratin genes K5 and K14 and directing epidermal cell fate.Romano RA et al
209724382010A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.Rothman N et al
116414042002The p53 family member genes are involved in the Notch signal pathway.Sasaki Y et al
215252442011C4orf41 and TTC-15 are mammalian TRAPP components with a role at an early stage in ER-to-Golgi trafficking.Scrivens PJ et al
119711802002TAp63gamma (p51A) and dNp63alpha (p73L), two major isoforms of the p63 gene, exert opposite effects on the vascular endothelial growth factor (VEGF) gene expression.Senoo M et al
217988932011The mutational landscape of head and neck squamous cell carcinoma.Stransky N et al
195705152009TAp63 prevents premature aging by promoting adult stem cell maintenance.Su X et al
85217301995Isolation and mapping of the human EIF4A2 gene homologous to the murine protein synthesis initiation factor 4A-II gene Eif4a2.Sudo K et al
171728582006Identification of new p63 targets in human keratinocytes.Testoni B et al
186605132008Cataloging and organizing p73 interactions in cell cycle arrest and apoptosis.Tozluoğlu M et al
214719852011p63, a story of mice and men.Vanbokhoven H et al
172972972007Hitting the numbers: the emerging network of p63 targets.Viganò MA et al
26699581989Fatty acid synthase, a proficient multifunctional enzyme.Wakil SJ et al
88043071996Diversity and specialization of mammalian SWI/SNF complexes.Wang W et al
150339062004p63: Molecular complexity in development and cancer.Westfall MD et al
215588032011UBE4B, a ubiquitin chain assembly factor, is required for MDM2-mediated p53 polyubiquitination and degradation.Wu H et al
213178852011UBE4B promotes Hdm2-mediated degradation of the tumor suppressor p53.Wu H et al
97749691998p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities.Yang A et al
215760892011ΔNp63 versatilely regulates a Broad NF-κB gene program and promotes squamous epithelial proliferation, migration, and inflammation.Yang X et al
114633912001PUMA induces the rapid apoptosis of colorectal cancer cells.Yu J et al
202250932010p63 short isoforms are found in invasive carcinomas only and not in benign breast Biase D et al
82427521993WAF1, a potential mediator of p53 tumor suppression.el-Deiry WS et al
114621732001p63 Gene mutations in eec syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation.van Bokhoven H et al

Other Information

Locus ID:

NCBI: 8626
MIM: 603273
HGNC: 15979
Ensembl: ENSG00000073282


dbSNP: 8626
ClinVar: 8626
TCGA: ENSG00000073282


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
TP53 Regulates Metabolic GenesREACTOMER-HSA-5628897
Programmed Cell DeathREACTOMER-HSA-5357801
Intrinsic Pathway for ApoptosisREACTOMER-HSA-109606
Activation of BH3-only proteinsREACTOMER-HSA-114452
Activation of PUMA and translocation to mitochondriaREACTOMER-HSA-139915
TP53 Regulates Transcription of Cell Death GenesREACTOMER-HSA-5633008
TP53 Regulates Transcription of Death Receptors and LigandsREACTOMER-HSA-6803211
TP53 Regulates Transcription of Genes Involved in Cytochrome C ReleaseREACTOMER-HSA-6803204
TP53 Regulates Transcription of Caspase Activators and CaspasesREACTOMER-HSA-6803207
TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertainREACTOMER-HSA-6803205
Regulation of TP53 ActivityREACTOMER-HSA-5633007
Regulation of TP53 Activity through Association with Co-factorsREACTOMER-HSA-6804759

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
193451892009A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis.344
209628482010TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs.200
167150762006p63 regulates an adhesion programme and cell survival in epithelial cells.185
164134712006p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis.179
201005812010Whole genome association study of brain-wide imaging phenotypes for identifying quantitative trait loci in MCI and AD: A study of the ADNI cohort.169
184834912008miR-203 represses 'stemness' by repressing DeltaNp63.167
166188082006Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation.151
171880342006Relationships between p63 binding, DNA sequence, transcription activity, and biological function in human cells.146
229496502012Loss of p63 and its microRNA-205 target results in enhanced cell migration and metastasis in prostate cancer.130
126401122003The Delta Np63 alpha phosphoprotein binds the p21 and 14-3-3 sigma promoters in vivo and has transcriptional repressor activity that is reduced by Hay-Wells syndrome-derived mutations.126


Austin Mattox ; Zhong Chen ; Carter Van Waes

TP63 (tumor protein p63)

Atlas Genet Cytogenet Oncol Haematol. 2012-12-01

Online version: