TP63


TP63
Tumor protein p63

C-terminal domain of the p63 protein
PDB rendering based on 1rg6.
Identifiers
Symbols TP63; AIS; B(p51A); B(p51B); EEC3; KET; LMS; NBP; OFC8; RHS; SHFM4; TP53CP; TP53L; TP73L; p40; p51; p53CP; p63; p73H; p73L
External IDs OMIM603273 MGI1330810 HomoloGene31189 GeneCards: TP63 Gene
RNA expression pattern
PBB GE TP73L 209863 s at tn.png
PBB GE TP73L 211194 s at tn.png
PBB GE TP73L 211195 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 8626 22061
Ensembl ENSG00000073282 ENSMUSG00000022510
UniProt Q9H3D4 O88898
RefSeq (mRNA) NM_001114978.1 NM_011641
RefSeq (protein) NP_001108450.1 NP_035771
Location (UCSC) Chr 3:
189.35 – 189.62 Mb
Chr 16:
25.68 – 25.89 Mb
PubMed search [1] [2]

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]

Contents

Function

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

Mutations in the TP63 gene are associated with ectrodactyly-ectodermal dysplasia-cleft syndrome, Hay–Wells syndrome, cleft lip/palate syndrome 3 (EEC3); split-hand/foot malformation 4 (SHFM4); ankyloblepharon-ectodermal defects-cleft lip/palate; ADULT syndrome (acro-dermato-ungual-lacrimal-tooth); limb-mammary syndrome; Rap-Hodgkin syndrome (RHS); and orofacial cleft 8.

Diagnostic utility

p63 immunostaining has utility for differentiating prostatic adenocarcinoma (the most common type of prostate cancer) and benign prostatic tissue;[11] normal prostatic glands stain with p63 (as they have basal cells), while the malignant glands in prostatic adenocarcinoma (which lacks these cells) do not.[12] 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.[13]

Interactions

TP63 has been shown to interact with HNRPAB.[14]

Regulation

There is some evidence that the expression of p63 is regulated by the microRNA miR-203.[15][16]

See also

  • AMACR - another marker for prostate adenocarcinoma


References

  1. ^ 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. Cell 2 (3): 305–16. doi:10.1016/S1097-2765(00)80275-0. PMID 9774969. 
  2. ^ 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. PMID 9662378. 
  3. ^ Zeng X, Zhu Y, Lu H (February 2001). "NBP is the p53 homolog p63". Carcinogenesis 22 (2): 215–9. doi:10.1093/carcin/22.2.215. PMID 11181441. 
  4. ^ 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". Carcinogenesis 22 (2): 295–300. doi:10.1093/carcin/22.2.295. PMID 11181451. 
  5. ^ 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. PMID 12750249. 
  6. ^ Skipper M (January 2007). "Dedicated protection for the female germline". Nature Reviews Molecular Cell Biology 8 (1): 4–5. doi:10.1038/nrm2091. 
  7. ^ Crum CP, McKeon FD (2010). "p63 in epithelial survival, germ cell surveillance, and neoplasia". Annu Rev Pathol 5: 349–71. doi:10.1146/annurev-pathol-121808-102117. PMID 20078223. 
  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. doi:10.1016/j.cell.2011.01.013. PMC 3087504. PMID 21335238. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3087504. 
  9. ^ Rouleau M, Medawar A, Hamon L, Shivtiel S, Wolchinsky Z, Zhou H, De Rosa L, Candi E, de la Forest Divonne S, Mikkola ML, van Bokhoven H, Missero C, Melino G, Pucéat M, Aberdam D (September 2011). "TAp63 is Important for Cardiac Differentiation of Embryonic Stem Cells and Heart Development". Stem Cells 29: 1612–1683. doi:10.1002/stem.723. PMID 21898690. http://minus.com/lNWTY9g2q5yYG. 
  10. ^ Su X, Paris M, Gi YJ, Tsai KY, Cho MS, Lin YL, Biernaskie JA, Sinha S, Prives C, Pevny LH, Miller FD, Flores ER (July 2009). "TAp63 prevents premature aging by promoting adult stem cell maintenance". Cell Stem Cell 5 (1): 64–75. doi:10.1016/j.stem.2009.04.003. PMID 19570515. 
  11. ^ 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. Malaysia 62 (1): 36–9. PMID 17682568. 
  12. ^ 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. PMID 17527076. 
  13. ^ 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. PMID 15309021. 
  14. ^ 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 Chem 278 (26): 23906–14. doi:10.1074/jbc.M300746200. PMID 12692135. 
  15. ^ Yi R, Poy MN, Stoffel M, Fuchs E (March 2008). "A skin microRNA promotes differentiation by repressing 'stemness'". Nature 452 (7184): 225–9. doi:10.1038/nature06642. PMID 18311128. 
  16. ^ Aberdam D, Candi E, Knight RA, Melino G (December 2008). "miRNAs, 'stemness' and skin". Trends Biochem. Sci. 33 (12): 583–91. doi:10.1016/j.tibs.2008.09.002. PMID 18848452. http://min.us/lGvvAc29SY8ux. 

Further reading

  • Shalom-Feuerstein R, Lena AM, Zhou H, De La Forest Divonne S, Van Bokhoven H, Candi E, Melino G, Aberdam D. ΔNp63 is an ectodermal gatekeeper of epidermal morphogenesis. Cell Death Differ. 2011 May;18(5):887-96. Link

External links


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