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Title: Tp63  
Author: World Heritage Encyclopedia
Language: English
Subject: Limb–mammary syndrome, Structure specific recognition protein 1, Atrichia with papular lesions, P53, Postreplication checkpoint
Publisher: World Heritage Encyclopedia


Tumor protein p63 also known as transformation-related protein 63 is a protein that in humans is encoded by the TP63 gene.[1][2][3][4]

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.[5] 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.[6]


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.[7] In contrast, TAp63 has been mostly restricted to its apoptotic function and more recently as the guardian of oocyte integrity.[8] Recently, two new functions have been attributed to TAp63 in heart development[9] and premature aging.[10]

Clinical significance

TP63 mutations underlie several malformation syndromes that include cleft lip and/or palate as a hallmark feature.[11] Mutations in the TP63 gene are associated with ectrodactyly-ectodermal dysplasia-cleft syndrome in which a midline cleft lip is a common feature,[11] cleft lip/palate syndrome 3 (EEC3); ectrodactyly (also known as split-hand/foot malformation 4 (SHFM4)); ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) or Hay–Wells syndrome in which a midline cleft lip is also a common feature,[11] Acro–dermato–ungual–lacrimal–tooth syndrome (ADULT); limb-mammary syndrome; Rap-Hodgkin syndrome (RHS); and orofacial cleft 8. Both cleft lip with or without a cleft palate and cleft palate only features have been seen to segregate within the same family with a TP63 mutation.[11] Recently, induced pluripotent stem cells have be produced from patients affected by EEC syndromes by cell reprogramming. The defective epithelial commitment could be partially rescued by a small therapeutic compound.[12]

Diagnostic utility

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;[13] normal prostatic glands stain with p63 (as they have basal cells), while the malignant glands in prostatic adenocarcinoma (which lacks these cells) do not.[14] 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.[15]


TP63 has been shown to interact with HNRPAB.[16] It also activates IRF6 transcription through the IRF6 enhancer element.[11]


There is some evidence that the expression of p63 is regulated by the microRNA miR-203.[17][18]

See also

  • AMACR - another marker for prostate adenocarcinoma


  1. ^ van Bokhoven H, Brunner HG (2002). "Splitting p63.". Am. J. Hum. Genet. 71 (1): 1–13.  
  2. ^ Brunner HG, Hamel BC, Bokhoven Hv H (2003). "P63 gene mutations and human developmental syndromes.". Am. J. Med. Genet. 112 (3): 284–90.  
  3. ^ 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 psychiatry 10 (5): 443–55.  
  4. ^ Zusman I (2005). "The soluble p51 protein in cancer diagnosis, prevention and therapy.". In Vivo 19 (3): 591–8.  
  5. ^ Morasso MI, Radoja N (2005). "Dlx genes, p63, and ectodermal dysplasias.". Birth Defects Res. C Embryo Today 75 (3): 163–71.  
  6. ^ Barbieri CE, Pietenpol JA (2006). "p63 and epithelial biology.". Exp. Cell Res. 312 (6): 695–706.  
  7. ^ 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 differentiation 18 (5): 887–96.  
  8. ^ Deutsch GB, Zielonka EM, Coutandin D, Weber TA, Schäfer B, Hannewald J, Luh LM, Durst FG, Ibrahim M, Hoffmann J, Niesen FH, Sentürk A, Kunkel H, Brutschy B, Schleiff E, Knapp S, Acker-Palmer A, Grez M, McKeon F, Dötsch V (February 2011). "DNA damage in oocytes induces a switch of the quality control factor TAp63α from dimer to tetramer". Cell 144 (4): 566–76.  
  9. ^  
  10. ^  
  11. ^ a b c d e PDB gallery. 
  12. ^ 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.
  13. ^  
  14. ^  
  15. ^  
  16. ^  
  17. ^  
  18. ^ Aberdam D, Candi E, Knight RA, Melino G (December 2008). "miRNAs, 'stemness' and skin". Trends Biochem. Sci. 33 (12): 583–91.  

Further reading

External links

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