Tumor protein p63 also known as transformation-related protein 63 is a protein that in humans is encoded by the TP63gene.
TP63 also known as the p63 gene was discovered 20 years after the discovery of the p53 tumor suppressor gene and along with p73 constitutes the p53 gene family based on their structural similarity. Despite being discovered significantly later than p53, phylogenetic analysis of p53, p63 and p73, suggest that p63 was the original member of the family from which p53 and p73 evolved.
Tumor protein p63 is a member of the p53 family of transcription factors. p63 -/- mice have several developmental defects which include the lack of limbs and other tissues, such as teeth and mammary glands, which develop as a result of interactions between mesenchyme and epithelium. TP63 encodes for two main isoforms by alternative promoters (TAp63 and ΔNp63). ΔNp63 is involved in multiple functions during skin development and in adult stem/progenitor cell regulation. In contrast, TAp63 has been mostly restricted to its apoptotic function and more recently as the guardian of oocyte integrity. Recently, two new functions have been attributed to TAp63 in heart development and premature aging.
p63 immunostaining has utility for head and neck squamous cell carcinomas, differentiating prostatic adenocarcinoma (the most common type of prostate cancer) and benign prostatic tissue; normal prostatic glands stain with p63 (as they have basal cells), while the malignant glands in prostatic adenocarcinoma (which lacks these cells) do not. P63 is also helpful in distinguishing poorly differentiated squamous cell carcinoma from small cell carcinoma or adenocarcinoma. P63 should be strongly stained in poorly differentiated squamous cell, but negative in small cell or adenocarcinoma.
^Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dötsch V, Andrews NC, Caput D, McKeon F (September 1998). "p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities". Mol. Cell2 (3): 305–16. doi:10.1016/S1097-2765(00)80275-0. PMID9774969.
^Osada M, Ohba M, Kawahara C, Ishioka C, Kanamaru R, Katoh I, Ikawa Y, Nimura Y, Nakagawara A, Obinata M, Ikawa S (July 1998). "Cloning and functional analysis of human p51, which structurally and functionally resembles p53". Nat. Med.4 (7): 839–43. doi:10.1038/nm0798-839. PMID9662378.
^Tan M, Bian J, Guan K, Sun Y (February 2001). "p53CP is p51/p63, the third member of the p53 gene family: partial purification and characterization". Carcinogenesis22 (2): 295–300. doi:10.1093/carcin/22.2.295. PMID11181451.
^Wu G, Nomoto S, Hoque MO, Dracheva T, Osada M, Lee CC, Dong SM, Guo Z, Benoit N, Cohen Y, Rechthand P, Califano J, Moon CS, Ratovitski E, Jen J, Sidransky D, Trink B (May 2003). "DeltaNp63alpha and TAp63alpha regulate transcription of genes with distinct biological functions in cancer and development". Cancer Res.63 (10): 2351–7. PMID12750249.
^Skipper M (January 2007). "Dedicated protection for the female germline". Nature Reviews Molecular Cell Biology8 (1): 4–5. doi:10.1038/nrm2091.
^Shalom Feuerstein R. et al. Impaired epithelial differentiation of induced pluripotent stem cells from EEC patients is rescued by APR-246/PRIMA-1MET. P.N.A.S 2012. http://minus.com/lbmC3TVGDx350s
^Shiran MS, Tan GC, Sabariah AR, Rampal L, Phang KS (March 2007). "p63 as a complementary basal cell specific marker to high molecular weight-cytokeratin in distinguishing prostatic carcinoma from benign prostatic lesions". Med. J. Malaysia62 (1): 36–9. PMID17682568.
^Herawi M, Epstein JI (June 2007). "Immunohistochemical antibody cocktail staining (p63/HMWCK/AMACR) of ductal adenocarcinoma and Gleason pattern 4 cribriform and noncribriform acinar adenocarcinomas of the prostate". Am. J. Surg. Pathol.31 (6): 889–94. doi:10.1097/01.pas.0000213447.16526.7f. PMID17527076.
^Zhang H, Liu J, Cagle PT, Allen TC, Laga AC, Zander DS (January 2005). "Distinction of pulmonary small cell carcinoma from poorly differentiated squamous cell carcinoma: an immunohistochemical approach". Mod. Pathol.18 (1): 111–8. doi:10.1038/modpathol.3800251. PMID15309021.
^Fomenkov A, Huang YP, Topaloglu O, Brechman A, Osada M, Fomenkova T et al. (2003). "P63 alpha mutations lead to aberrant splicing of keratinocyte growth factor receptor in the Hay-Wells syndrome.". J Biol Chem278 (26): 23906–14. doi:10.1074/jbc.M300746200. PMID12692135.CS1 maint: Explicit use of et al. (link)
^Yi R, Poy MN, Stoffel M, Fuchs E (March 2008). "A skin microRNA promotes differentiation by repressing 'stemness'". Nature452 (7184): 225–9. doi:10.1038/nature06642. PMID18311128.
Brunner HG, Hamel BC, Bokhoven Hv H (2003). "P63 gene mutations and human developmental syndromes.". Am. J. Med. Genet.112 (3): 284–90. doi:10.1002/ajmg.10778. PMID12357472.
Jacobs WB, Walsh GS, Miller FD (2005). "Neuronal survival and p73/p63/p53: a family affair.". The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry10 (5): 443–55. doi:10.1177/1073858404263456. PMID15359011.
Zusman I (2005). "The soluble p51 protein in cancer diagnosis, prevention and therapy.". In Vivo19 (3): 591–8. PMID15875781.
Shalom-Feuerstein, R; Lena, AM; Zhou, H; De La Forest Divonne, S; Van Bokhoven, H; Candi, E; Melino, G; Aberdam, D (May 2011). "ΔNp63 is an ectodermal gatekeeper of epidermal morphogenesis.". Cell death and differentiation18 (5): 887–96. doi:10.1038/cdd.2010.159. PMID21127502.Cite uses deprecated parameter |coauthors= (help)