Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

TP63 (tumor protein p63)

Written2012-12Austin 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

(Note : for Links provided by Atlas : click)


HGNC (Hugo) TP63
HGNC Alias symbp51
HGNC Previous nameTP73L
HGNC Previous nametumor protein p73-like
 tumor protein p53-like
 tumor protein p53-competing protein
LocusID (NCBI) 8626
Atlas_Id 365
Location 3q28  [Link to chromosome band 3q28]
Location_base_pair Starts at 189631389 and ends at 189897275 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping TP63.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
B3GALNT1 (3q26.1)::TP63 (3q28)GABARAPL2 (16q23.1)::TP63 (3q28)IL1RAP (3q28)::TP63 (3q28)
LPP (3q28)::TP63 (3q28)MAN2B2 (4p16.1)::TP63 (3q28)P3H2 (3q28)::TP63 (3q28)
TBL1XR1 (3q26.32)::TP63 (3q28)TMEM110 (3p21.1)::TP63 (3q28)TNRC6B (22q13.1)::TP63 (3q28)
TP63 (3q28)::MVK (12q24.11)TP63 (3q28)::TBL1XR1 (3q26.32)ZMAT3 (3q26.32)::TP63 (3q28)


Note 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.
Description 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.


  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**.
Description 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).

Expression 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).
Localisation As a transcription factor, p63 is normally present in the nucleus (Yang et al., 1998).
Function 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. It's 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; D'Erchia 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 (D'Erchia 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).
Homology 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 Various cancers
Note 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 Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome
Note 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 Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3)
Note 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 Hay-Wells syndrome
Note 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 Limb-mammary syndrome (LMS)
Note 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).

To be noted

Acknowledgements: supported by NIDCD Intramural Project ZIA-DC-000073 and 74.


EEC syndrome type 3 with a heterozygous germline mutation in the P63 gene and B cell lymphoma.
Akahoshi K, Sakazume S, Kosaki K, Ohashi H, Fukushima Y.
Am J Med Genet A. 2003 Jul 30;120A(3):370-3.
PMID 12838557
Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway.
Akira S, Nishio Y, Inoue M, Wang XJ, Wei S, Matsusaka T, Yoshida K, Sudo T, Naruto M, Kishimoto T.
Cell. 1994 Apr 8;77(1):63-71.
PMID 7512451
Cloning and chromosomal mapping of the human p53-related KET gene to chromosome 3q27 and its murine homolog Ket to mouse chromosome 16.
Augustin M, Bamberger C, Paul D, Schmale H.
Mamm Genome. 1998 Nov;9(11):899-902.
PMID 9799841
Properties of the receptor for epidermal growth factor.
Carpenter G.
Cell. 1984 Jun;37(2):357-8.
PMID 6327062
p63 regulates an adhesion programme and cell survival in epithelial cells.
Carroll DK, Carroll JS, Leong CO, Cheng F, Brown M, Mills AA, Brugge JS, Ellisen LW.
Nat Cell Biol. 2006 Jun;8(6):551-61. Epub 2006 May 21.
PMID 16715076
The prespliceosome components SAP 49 and SAP 145 interact in a complex implicated in tethering U2 snRNP to the branch site.
Champion-Arnaud P, Reed R.
Genes Dev. 1994 Aug 15;8(16):1974-83.
PMID 7958871
Structures of p63 DNA binding domain in complexes with half-site and with spacer-containing full response elements.
Chen C, Gorlatova N, Kelman Z, Herzberg O.
Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6456-61. doi: 10.1073/pnas.1013657108. Epub 2011 Apr 4.
PMID 21464285
Expression of p63 protein and mRNA in oral epithelial dysplasia.
Chen YK, Hsue SS, Lin LM.
J Oral Pathol Med. 2005 Apr;34(4):232-9.
PMID 15752259
p53-family proteins and their regulators: hubs and spokes in tumor suppression.
Collavin L, Lunardi A, Del Sal G.
Cell Death Differ. 2010 Jun;17(6):901-11. doi: 10.1038/cdd.2010.35. Epub 2010 Apr 9.
PMID 20379196
The fatty acid synthase gene is a conserved p53 family target from worm to human.
D'Erchia AM, Tullo A, Lefkimmiatis K, Saccone C, Sbisa E.
Cell Cycle. 2006 Apr;5(7):750-8. Epub 2006 Apr 1.
PMID 16582625
p73 and p63 are homotetramers capable of weak heterotypic interactions with each other but not with p53.
Davison TS, Vagner C, Kaghad M, Ayed A, Caput D, Arrowsmith CH.
J Biol Chem. 1999 Jun 25;274(26):18709-14.
PMID 10373484
p63 and p73, the ancestors of p53.
Dotsch V, Bernassola F, Coutandin D, Candi E, Melino G.
Cold Spring Harb Perspect Biol. 2010 Sep;2(9):a004887. doi: 10.1101/cshperspect.a004887. Epub 2010 May 19.
PMID 20484388
Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia.
Ellinghaus E, Stanulla M, Richter G, Ellinghaus D, te Kronnie G, Cario G, Cazzaniga G, Horstmann M, Panzer Grumayer R, Cave H, Trka J, Cinek O, Teigler-Schlegel A, ElSharawy A, Hasler R, Nebel A, Meissner B, Bartram T, Lescai F, Franceschi C, Giordan M, Nurnberg P, Heinzow B, Zimmermann M, Schreiber S, Schrappe M, Franke A.
Leukemia. 2012 May;26(5):902-9. doi: 10.1038/leu.2011.302. Epub 2011 Nov 11.
PMID 22076464
p63 and p73 are required for p53-dependent apoptosis in response to DNA damage.
Flores ER, Tsai KY, Crowley D, Sengupta S, Yang A, McKeon F, Jacks T.
Nature. 2002 Apr 4;416(6880):560-4.
PMID 11932750
Absence of integrin alpha 6 leads to epidermolysis bullosa and neonatal death in mice.
Georges-Labouesse E, Messaddeq N, Yehia G, Cadalbert L, Dierich A, Le Meur M.
Nat Genet. 1996 Jul;13(3):370-3.
PMID 8673141
Human ligands of the Notch receptor.
Gray GE, Mann RS, Mitsiadis E, Henrique D, Carcangiu ML, Banks A, Leiman J, Ward D, Ish-Horowitz D, Artavanis-Tsakonas S.
Am J Pathol. 1999 Mar;154(3):785-94.
PMID 10079256
Exon 6 of human Jagged-1 encodes an autonomously folding unit.
Guarnaccia C, Pintar A, Pongor S.
FEBS Lett. 2004 Sep 10;574(1-3):156-60.
PMID 15358557
The syndrome of ankyloblepharon, ectodermal defects and cleft lip and palate: an autosomal dominant condition.
Hay RJ, Wells RS.
Br J Dermatol. 1976 Mar;94(3):277-89.
PMID 946410
Gadd45a regulates matrix metalloproteinases by suppressing DeltaNp63alpha and beta-catenin via p38 MAP kinase and APC complex activation.
Hildesheim J, Belova GI, Tyner SD, Zhou X, Vardanian L, Fornace AJ Jr.
Oncogene. 2004 Mar 11;23(10):1829-37.
PMID 14647429
A genome-wide association study identifies two new lung cancer susceptibility loci at 13q12.12 and 22q12.2 in Han Chinese.
Hu Z, Wu C, Shi Y, Guo H, Zhao X, Yin Z, Yang L, Dai J, Hu L, Tan W, Li Z, Deng Q, Wang J, Wu W, Jin G, Jiang Y, Yu D, Zhou G, Chen H, Guan P, Chen Y, Shu Y, Xu L, Liu X, Liu L, Xu P, Han B, Bai C, Zhao Y, Zhang H, Yan Y, Ma H, Chen J, Chu M, Lu F, Zhang Z, Chen F, Wang X, Jin L, Lu J, Zhou B, Lu D, Wu T, Lin D, Shen H.
Nat Genet. 2011 Jul 3;43(8):792-6. doi: 10.1038/ng.875.
PMID 21725308
Global tumor protein p53/p63 interactome: making a case for cisplatin chemoresistance.
Huang Y, Jeong JS, Okamura J, Sook-Kim M, Zhu H, Guerrero-Preston R, Ratovitski EA.
Cell Cycle. 2012 Jun 15;11(12):2367-79. doi: 10.4161/cc.20863. Epub 2012 Jun 15.
PMID 22672905
Epidermal growth factor receptor signaling is required for normal ovarian steroidogenesis and oocyte maturation.
Jamnongjit M, Gill A, Hammes SR.
Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16257-62. Epub 2005 Oct 31.
PMID 16260720
p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation.
Laurikkala J, Mikkola ML, James M, Tummers M, Mills AA, Thesleff I.
Development. 2006 Apr;133(8):1553-63. Epub 2006 Mar 8.
PMID 16524929
The p63/p73 network mediates chemosensitivity to cisplatin in a biologically defined subset of primary breast cancers.
Leong CO, Vidnovic N, DeYoung MP, Sgroi D, Ellisen LW.
J Clin Invest. 2007 May;117(5):1370-80. Epub 2007 Apr 19.
PMID 17446929
Chromosomal mapping of human keratin genes: evidence of non-linkage.
Lessin SR, Huebner K, Isobe M, Croce CM, Steinert PM.
J Invest Dermatol. 1988 Dec;91(6):572-8.
PMID 2461420
TNF-a promotes c-REL/DeltaNp63a interaction and TAp73 dissociation from key genes that mediate growth arrest and apoptosis in head and neck cancer.
Lu H, Yang X, Duggal P, Allen CT, Yan B, Cohen J, Nottingham L, Romano RA, Sinha S, King KE, Weinberg WC, Chen Z, Van Waes C.
Cancer Res. 2011 Nov 1;71(21):6867-77. doi: 10.1158/0008-5472.CAN-11-2460. Epub 2011 Sep 20.
PMID 21933882
EEC syndrome and genitourinary anomalies: an update.
Maas SM, de Jong TP, Buss P, Hennekam RC.
Am J Med Genet. 1996 Jun 14;63(3):472-8.
PMID 8737655
Identification and functional characterization of two new transcriptional variants of the human p63 gene.
Mangiulli M, Valletti A, Caratozzolo MF, Tullo A, Sbisa E, Pesole G, D'Erchia AM.
Nucleic Acids Res. 2009 Oct;37(18):6092-104. doi: 10.1093/nar/gkp674. Epub 2009 Aug 21.
PMID 19700772
Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of p63.
McGrath JA, Duijf PH, Doetsch V, Irvine AD, de Waal R, Vanmolkot KR, Wessagowit V, Kelly A, Atherton DJ, Griffiths WA, Orlow SJ, van Haeringen A, Ausems MG, Yang A, McKeon F, Bamshad MA, Brunner HG, Hamel BC, van Bokhoven H.
Hum Mol Genet. 2001 Feb 1;10(3):221-9.
PMID 11159940
p63 and the epithelial stem cell: more than status quo?
McKeon F.
Genes Dev. 2004 Mar 1;18(5):465-9.
PMID 15037544
IL-6 trans-signaling via STAT3 directs T cell infiltration in acute inflammation.
McLoughlin RM, Jenkins BJ, Grail D, Williams AS, Fielding CA, Parker CR, Ernst M, Topley N, Jones SA.
Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9589-94. Epub 2005 Jun 23.
PMID 15976028
p63 is a p53 homologue required for limb and epidermal morphogenesis.
Mills AA, Zheng B, Wang XJ, Vogel H, Roop DR, Bradley A.
Nature. 1999 Apr 22;398(6729):708-13.
PMID 10227293
p63 and p73: roles in development and tumor formation.
Moll UM, Slade N.
Mol Cancer Res. 2004 Jul;2(7):371-86.
PMID 15280445
The DNA sequence, annotation and analysis of human chromosome 3.
Muzny DM, Scherer SE, Kaul R, Wang J, Yu J, Sudbrak R, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Wei S, Wheeler DA, Wright MW, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clendenning J, Clerc-Blankenburg KP, Chen R, Chen Z, Davis C, Delgado O, Dinh HH, Dong W, Draper H, Ernst S, Fu G, Gonzalez-Garay ML, Garcia DK, Gillett W, Gu J, Hao B, Haugen E, Havlak P, He X, Hennig S, Hu S, Huang W, Jackson LR, Jacob LS, Kelly SH, Kube M, Levy R, Li Z, Liu B, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Palmeiri A, Pasternak S, Perez LM, Phelps KA, Plopper FJ, Qiang B, Raymond C, Rodriguez R, Saenphimmachak C, Santibanez J, Shen H, Shen Y, Subramanian S, Tabor PE, Verduzco D, Waldron L, Wang J, Wang J, Wang Q, Williams GA, Wong GK, Yao Z, Zhang J, Zhang X, Zhao G, Zhou J, Zhou Y, Nelson D, Lehrach H, Reinhardt R, Naylor SL, Yang H, Olson M, Weinstock G, Gibbs RA.
Nature. 2006 Apr 27;440(7088):1194-8.
PMID 16641997
Structure and kinetic stability of the p63 tetramerization domain.
Natan E, Joerger AC.
J Mol Biol. 2012 Jan 20;415(3):503-13. doi: 10.1016/j.jmb.2011.11.007. Epub 2011 Nov 12.
PMID 22100306
Comprehensive mutational analysis and mRNA isoform quantification of TP63 in normal and neoplastic human prostate cells.
Parsons JK, Saria EA, Nakayama M, Vessella RL, Sawyers CL, Isaacs WB, Faith DA, Bova GS, Samathanam CA, Mitchell R, De Marzo AM.
Prostate. 2009 Apr 1;69(5):559-69. doi: 10.1002/pros.20904.
PMID 19142959
DeltaNp63 induces beta-catenin nuclear accumulation and signaling.
Patturajan M, Nomoto S, Sommer M, Fomenkov A, Hibi K, Zangen R, Poliak N, Califano J, Trink B, Ratovitski E, Sidransky D.
Cancer Cell. 2002 May;1(4):369-79.
PMID 12086851
Transcriptional programs regulated by p63 in normal epithelium and tumors.
Perez CA, Pietenpol JA.
Cell Cycle. 2007 Feb 1;6(3):246-54. Epub 2007 Feb 3.
PMID 17297308
ADULT-syndrome: an autosomal-dominant disorder with pigment anomalies, ectrodactyly, nail dysplasia, and hypodontia.
Propping P, Zerres K.
Am J Med Genet. 1993 Mar 1;45(5):642-8.
PMID 8456838
Further phenotypic and genetic variation in ADULT syndrome.
Reisler TT, Patton MA, Meagher PP.
Am J Med Genet A. 2006 Nov 15;140(22):2495-500.
PMID 17041931
Five SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin (SMARC) genes are dispersed in the human genome.
Ring HZ, Vameghi-Meyers V, Wang W, Crabtree GR, Francke U.
Genomics. 1998 Jul 1;51(1):140-3.
PMID 9693044
Delineation of the ADULT syndrome phenotype due to arginine 298 mutations of the p63 gene.
Rinne T, Spadoni E, Kjaer KW, Danesino C, Larizza D, Kock M, Huoponen K, Savontaus ML, Aaltonen M, Duijf P, Brunner HG, Penttinen M, van Bokhoven H.
Eur J Hum Genet. 2006 Aug;14(8):904-10. Epub 2006 May 17.
PMID 16724007
p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis.
Rocco JW, Leong CO, Kuperwasser N, DeYoung MP, Ellisen LW.
Cancer Cell. 2006 Jan;9(1):45-56.
PMID 16413471
An active role of the DeltaN isoform of p63 in regulating basal keratin genes K5 and K14 and directing epidermal cell fate.
Romano RA, Ortt K, Birkaya B, Smalley K, Sinha S.
PLoS One. 2009 May 20;4(5):e5623. doi: 10.1371/journal.pone.0005623.
PMID 19461998
A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.
Rothman N, Garcia-Closas M, Chatterjee N, Malats N, Wu X, Figueroa JD, Real FX, Van Den Berg D, Matullo G, Baris D, Thun M, Kiemeney LA, Vineis P, De Vivo I, Albanes D, Purdue MP, Rafnar T, Hildebrandt MA, Kiltie AE, Cussenot O, Golka K, Kumar R, Taylor JA, Mayordomo JI, Jacobs KB, Kogevinas M, Hutchinson A, Wang Z, Fu YP, Prokunina-Olsson L, Burdett L, Yeager M, Wheeler W, Tardon A, Serra C, Carrato A, Garcia-Closas R, Lloreta J, Johnson A, Schwenn M, Karagas MR, Schned A, Andriole G Jr, Grubb R 3rd, Black A, Jacobs EJ, Diver WR, Gapstur SM, Weinstein SJ, Virtamo J, Cortessis VK, Gago-Dominguez M, Pike MC, Stern MC, Yuan JM, Hunter DJ, McGrath M, Dinney CP, Czerniak B, Chen M, Yang H, Vermeulen SH, Aben KK, Witjes JA, Makkinje RR, Sulem P, Besenbacher S, Stefansson K, Riboli E, Brennan P, Panico S, Navarro C, Allen NE, Bueno-de-Mesquita HB, Trichopoulos D, Caporaso N, Landi MT, Canzian F, Ljungberg B, Tjonneland A, Clavel-Chapelon F, Bishop DT, Teo MT, Knowles MA, Guarrera S, Polidoro S, Ricceri F, Sacerdote C, Allione A, Cancel-Tassin G, Selinski S, Hengstler JG, Dietrich H, Fletcher T, Rudnai P, Gurzau E, Koppova K, Bolick SC, Godfrey A, Xu Z, Sanz-Velez JI, D Garcia-Prats M, Sanchez M, Valdivia G, Porru S, Benhamou S, Hoover RN, Fraumeni JF Jr, Silverman DT, Chanock SJ.
Nat Genet. 2010 Nov;42(11):978-84. doi: 10.1038/ng.687. Epub 2010 Oct 24.
PMID 20972438
The p53 family member genes are involved in the Notch signal pathway.
Sasaki Y, Ishida S, Morimoto I, Yamashita T, Kojima T, Kihara C, Tanaka T, Imai K, Nakamura Y, Tokino T.
J Biol Chem. 2002 Jan 4;277(1):719-24. Epub 2001 Oct 18.
PMID 11641404
C4orf41 and TTC-15 are mammalian TRAPP components with a role at an early stage in ER-to-Golgi trafficking.
Scrivens PJ, Noueihed B, Shahrzad N, Hul S, Brunet S, Sacher M.
Mol Biol Cell. 2011 Jun 15;22(12):2083-93. doi: 10.1091/mbc.E10-11-0873. Epub 2011 Apr 27.
PMID 21525244
TAp63gamma (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, Matsumura Y, Habu S.
Oncogene. 2002 Apr 11;21(16):2455-65.
PMID 11971180
The mutational landscape of head and neck squamous cell carcinoma.
Stransky N, Egloff AM, Tward AD, Kostic AD, Cibulskis K, Sivachenko A, Kryukov GV, Lawrence MS, Sougnez C, McKenna A, Shefler E, Ramos AH, Stojanov P, Carter SL, Voet D, Cortes ML, Auclair D, Berger MF, Saksena G, Guiducci C, Onofrio RC, Parkin M, Romkes M, Weissfeld JL, Seethala RR, Wang L, Rangel-Escareno C, Fernandez-Lopez JC, Hidalgo-Miranda A, Melendez-Zajgla J, Winckler W, Ardlie K, Gabriel SB, Meyerson M, Lander ES, Getz G, Golub TR, Garraway LA, Grandis JR.
Science. 2011 Aug 26;333(6046):1157-60. doi: 10.1126/science.1208130. Epub 2011 Jul 28.
PMID 21798893
TAp63 prevents premature aging by promoting adult stem cell maintenance.
Su X, Paris M, Gi YJ, Tsai KY, Cho MS, Lin YL, Biernaskie JA, Sinha S, Prives C, Pevny LH, Miller FD, Flores ER.
Cell Stem Cell. 2009 Jul 2;5(1):64-75. doi: 10.1016/j.stem.2009.04.003.
PMID 19570515
Isolation and mapping of the human EIF4A2 gene homologous to the murine protein synthesis initiation factor 4A-II gene Eif4a2.
Sudo K, Takahashi E, Nakamura Y.
Cytogenet Cell Genet. 1995;71(4):385-8.
PMID 8521730
Identification of new p63 targets in human keratinocytes.
Testoni B, Borrelli S, Tenedini E, Alotto D, Castagnoli C, Piccolo S, Tagliafico E, Ferrari S, Vigano MA, Mantovani R.
Cell Cycle. 2006 Dec;5(23):2805-11. Epub 2006 Dec 1.
PMID 17172858
Cataloging and organizing p73 interactions in cell cycle arrest and apoptosis.
Tozluoglu M, Karaca E, Haliloglu T, Nussinov R.
Nucleic Acids Res. 2008 Sep;36(15):5033-49. doi: 10.1093/nar/gkn481. Epub 2008 Jul 26.
PMID 18660513
p63, a story of mice and men.
Vanbokhoven H, Melino G, Candi E, Declercq W.
J Invest Dermatol. 2011 Jun;131(6):1196-207. doi: 10.1038/jid.2011.84. Epub 2011 Apr 7.
PMID 21471985
Hitting the numbers: the emerging network of p63 targets.
Vigano MA, Mantovani R.
Cell Cycle. 2007 Feb 1;6(3):233-9. Epub 2007 Feb 3.
PMID 17297297
Fatty acid synthase, a proficient multifunctional enzyme.
Wakil SJ.
Biochemistry. 1989 May 30;28(11):4523-30.
PMID 2669958
Diversity and specialization of mammalian SWI/SNF complexes.
Wang W, Xue Y, Zhou S, Kuo A, Cairns BR, Crabtree GR.
Genes Dev. 1996 Sep 1;10(17):2117-30.
PMID 8804307
p63: Molecular complexity in development and cancer.
Westfall MD, Pietenpol JA.
Carcinogenesis. 2004 Jun;25(6):857-64. Epub 2004 Mar 19.
PMID 15033906
UBE4B, a ubiquitin chain assembly factor, is required for MDM2-mediated p53 polyubiquitination and degradation.
Wu H, Leng RP.
Cell Cycle. 2011 Jun 15;10(12):1912-5. Epub 2011 Jun 15.
PMID 21558803
UBE4B promotes Hdm2-mediated degradation of the tumor suppressor p53.
Wu H, Pomeroy SL, Ferreira M, Teider N, Mariani J, Nakayama KI, Hatakeyama S, Tron VA, Saltibus LF, Spyracopoulos L, Leng RP.
Nat Med. 2011 Mar;17(3):347-55. doi: 10.1038/nm.2283. Epub 2011 Feb 13.
PMID 21317885
p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities.
Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dotsch V, Andrews NC, Caput D, McKeon F.
Mol Cell. 1998 Sep;2(3):305-16.
PMID 9774969
DeltaNp63 versatilely regulates a Broad NF-kB gene program and promotes squamous epithelial proliferation, migration, and inflammation.
Yang X, Lu H, Yan B, Romano RA, Bian Y, Friedman J, Duggal P, Allen C, Chuang R, Ehsanian R, Si H, Sinha S, Van Waes C, Chen Z.
Cancer Res. 2011 May 15;71(10):3688-700. doi: 10.1158/0008-5472.CAN-10-3445.
PMID 21576089
PUMA induces the rapid apoptosis of colorectal cancer cells.
Yu J, Zhang L, Hwang PM, Kinzler KW, Vogelstein B.
Mol Cell. 2001 Mar;7(3):673-82.
PMID 11463391
p63 short isoforms are found in invasive carcinomas only and not in benign breast conditions.
de Biase D, Morandi L, Degli Esposti R, Ligorio C, Pession A, Foschini MP, Eusebi V.
Virchows Arch. 2010 Apr;456(4):395-401. doi: 10.1007/s00428-010-0900-1. Epub 2010 Mar 12.
PMID 20225093
WAF1, a potential mediator of p53 tumor suppression.
el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B.
Cell. 1993 Nov 19;75(4):817-25.
PMID 8242752
p63 Gene mutations in eec syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation.
van Bokhoven H, Hamel BC, Bamshad M, Sangiorgi E, Gurrieri F, Duijf PH, Vanmolkot KR, van Beusekom E, van Beersum SE, Celli J, Merkx GF, Tenconi R, Fryns JP, Verloes A, Newbury-Ecob RA, Raas-Rotschild A, Majewski F, Beemer FA, Janecke A, Chitayat D, Crisponi G, Kayserili H, Yates JR, Neri G, Brunner HG.
Am J Hum Genet. 2001 Sep;69(3):481-92. Epub 2001 Jul 17.
PMID 11462173


This paper should be referenced as such :
Mattox, A ; Chen, Z ; Van, Waes C
TP63 (tumor protein p63)
Atlas Genet Cytogenet Oncol Haematol. 2013;17(6):414-420.
Free journal version : [ pdf ]   [ DOI ]

Other Leukemias implicated (Data extracted from papers in the Atlas) [ 4 ]
  Anaplastic large cell lymphoma, ALK-negative
Breast implant-associated anaplastic large cell lymphoma
inv(3)(q26q28) TBL1XR1::TP63
inv(3)(q26q28) TP63::TBL1XR1

External links

HGNC (Hugo)TP63   15979
LRG (Locus Reference Genomic)LRG_428
Entrez_Gene (NCBI)TP63    tumor protein p63
AliasesAIS; B(p51A); B(p51B); EEC3; 
KET; LMS; NBP; OFC8; RHS; SHFM4; TP53CP; TP53L; TP73L; p40; p51; p53CP; p63; p73H; p73L
GeneCards (Weizmann)TP63
Ensembl hg19 (Hinxton)ENSG00000073282 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000073282 [Gene_View]  ENSG00000073282 [Sequence]  chr3:189631389-189897275 [Contig_View]  TP63 [Vega]
ICGC DataPortalENSG00000073282
TCGA cBioPortalTP63
AceView (NCBI)TP63
Genatlas (Paris)TP63
SOURCE (Princeton)TP63
Genetics Home Reference (NIH)TP63
Genomic and cartography
GoldenPath hg38 (UCSC)TP63  -     chr3:189631389-189897275 +  3q28   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)TP63  -     3q28   [Description]    (hg19-Feb_2009)
GoldenPathTP63 - 3q28 [CytoView hg19]  TP63 - 3q28 [CytoView hg38]
Genome Data Viewer NCBITP63 [Mapview hg19]  
OMIM103285   106260   129400   603273   603543   604292   605289   618149   
Gene and transcription
Genbank (Entrez)AB010153 AB016072 AB016073 AB042841 AF075428
RefSeq transcript (Entrez)NM_001114978 NM_001114979 NM_001114980 NM_001114981 NM_001114982 NM_001329144 NM_001329145 NM_001329146 NM_001329148 NM_001329149 NM_001329150 NM_001329964 NM_003722
Consensus coding sequences : CCDS (NCBI)TP63
Gene ExpressionTP63 [ NCBI-GEO ]   TP63 [ EBI - ARRAY_EXPRESS ]   TP63 [ SEEK ]   TP63 [ MEM ]
Gene Expression Viewer (FireBrowse)TP63 [ Firebrowse - Broad ]
GenevisibleExpression of TP63 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)8626
GTEX Portal (Tissue expression)TP63
Human Protein AtlasENSG00000073282-TP63 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)TP63
Human Protein Atlas [tissue]ENSG00000073282-TP63 [tissue]
Protein Interaction databases
Ontologies - Pathways
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Oct 8 21:29:55 CEST 2021

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us