Role of p63 in Development, Tumorigenesis and Cancer Progression - Cancer Microenvironment
- ️Xiao, Zhi-Xiong
- ️Tue Jul 31 2012
Levine AJ, Oren M (2009) The first 30 years of p53: growing ever more complex. Nat Rev Cancer 9(10):749–758
Vousden KH, Prives C (2009) Blinded by the light: the growing complexity of p53. Cell 137(3):413–431
Yang A et al (1998) p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell 2(3):305–316
Kaghad M et al (1997) Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell 90(4):809–819
Melino G (2011) p63 is a suppressor of tumorigenesis and metastasis interacting with mutant p53. Cell Death Differ
Vanbokhoven H et al (2011) p63, a story of mice and men. J Invest Dermatol
Yang A et al (1999) p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 398(6729):714–718
May P, May E (1999) Twenty years of p53 research: structural and functional aspects of the p53 protein. Oncogene 18(53):7621–7636
Khoury MP, Bourdon J-C (2011) p53 isoforms: an intracellular microprocessor? Genes Cancer 2(4):453–465
Marcel V, Hainaut P (2009) p53 isoforms - a conspiracy to kidnap p53 tumor suppressor activity? Cell Mol Life Sci 66(3):391–406
Yang A et al (2000) p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours. Nature 404(6773):99–103
Weber A et al (2002) Expression of p53 and its homologues in primary and recurrent squamous cell carcinomas of the head and neck. Int J Cancer 99(1):22–28
Zawacka-Pankau J et al (2010) p73 tumor suppressor protein: a close relative of p53 not only in structure but also in anti-cancer approach? Cell Cycle 9(4)
Tomasini R et al (2008) TAp73 knockout shows genomic instability with infertility and tumor suppressor functions. Genes Dev 22(19):2677–2691
Deyoung MP, Ellisen LW (2007) p63 and p73 in human cancer: defining the network. Oncogene 26(36):5169–5183
Mills AA et al (1999) p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature 398(6729):708–713
Westfall MD et al (2003) The 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. Mol Cell Biol 23(7):2264–2276
Dohn M, Zhang S, Chen X (2001) p63alpha and DeltaNp63alpha can induce cell cycle arrest and apoptosis and differentially regulate p53 target genes. Oncogene 20(25):3193–3205
Ghioni P et al (2002) Complex transcriptional effects of p63 isoforms: identification of novel activation and repression domains. Mol Cell Biol 22(24):8659–8668
Helton ES, Zhu J, Chen X (2006) The unique NH2-terminally deleted (DeltaN) residues, the PXXP motif, and the PPXY motif are required for the transcriptional activity of the DeltaN variant of p63. J Biol Chem 281(5):2533–2542
Mangiulli M et al (2009) Identification and functional characterization of two new transcriptional variants of the human p63 gene. Nucleic Acids Res 37(18):6092–6104
Thanos CD, Bowie JU (1999) p53 Family members p63 and p73 are SAM domain-containing proteins. Protein Sci 8(8):1708–1710
Serber Z et al (2002) A C-terminal inhibitory domain controls the activity of p63 by an intramolecular mechanism. Mol Cell Biol 22(24):8601–8611
Coutandin D et al (2009) Conformational stability and activity of p73 require a second helix in the tetramerization domain. Cell Death Differ 16(12):1582–1589
Joerger A et al (2009) Structural evolution of p53, p63, and p73: implication for heterotetramer formation. Proc Natl Acad Sci USA
Gaiddon C et al (2001) A subset of tumor-derived mutant forms of p53 down-regulate p63 and p73 through a direct interaction with the p53 core domain. Mol Cell Biol 21(5):1874–1887
Rocco JW et al (2006) p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis. Cancer Cell 9(1):45–56
Davison TS et al (1999) p73 and p63 are homotetramers capable of weak heterotypic interactions with each other but not with p53. J Biol Chem 274(26):18709–18714
Ying H et al (2005) DNA-binding and transactivation activities are essential for TAp63 protein degradation. Mol Cell Biol 25(14):6154–6164
Barbareschi M et al (2001) p63, a p53 homologue, is a selective nuclear marker of myoepithelial cells of the human breast. Am J Surg Pathol 25(8):1054–1060
Signoretti S et al (2000) p63 is a prostate basal cell marker and is required for prostate development. Am J Pathol 157(6):1769–1775
Candi E et al (2007) DeltaNp63 regulates thymic development through enhanced expression of FgfR2 and Jag2. Proc Natl Acad Sci USA 104(29):11999–12004
Laurikkala J et al (2006) p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation. Development 133(8):1553–1563
Gonfloni S et al (2009) Inhibition of the c-Abl-TAp63 pathway protects mouse oocytes from chemotherapy-induced death. Nat Med 15(10):1179–1185
Suh E-K et al (2006) p63 protects the female germ line during meiotic arrest. Nature 444(7119):624–628
Barbieri CE et al (2006) Loss of p63 leads to increased cell migration and up-regulation of genes involved in invasion and metastasis. Cancer Res 66(15):7589–7597
Carroll DK et al (2006) p63 regulates an adhesion programme and cell survival in epithelial cells. Nat Cell Biol 8(6):551–561
Romano R-A et al (2009) An active role of the DeltaN isoform of p63 in regulating basal keratin genes K5 and K14 and directing epidermal cell fate. PLoS One 4(5):e5623
Ferretti E et al (2011) A conserved Pbx-Wnt-p63-Irf6 regulatory module controls face morphogenesis by promoting epithelial apoptosis. Dev Cell 21(4):627–641
Aberdam D et al (2007) Key role of p63 in BMP-4-induced epidermal commitment of embryonic stem cells. Cell Cycle 6(3):291–294
Mikkola ML (2007) p63 in skin appendage development. Cell Cycle 6(3):285–290
Herfs M et al (2010) Regulation of p63 isoforms by snail and slug transcription factors in human squamous cell carcinoma. Am J Pathol
Higashikawa K et al (2007) Snail-induced down-regulation of DeltaNp63alpha acquires invasive phenotype of human squamous cell carcinoma. Cancer Res 67(19):9207–9213
Petitjean A et al (2005) The expression of TA and DeltaNp63 are regulated by different mechanisms in liver cells. Oncogene 24(3):512–519
Yao J-Y, Pao C-C, Chen J-K (2010) Transcriptional activity of TAp63 promoter is regulated by c-jun. J Cell Physiol 225(3):898–904
Wu J et al (2010) TAp63 is a transcriptional target of NF-kappaB. J Cell Biochem 109(4):702–710
Lena A. et al (2008) miR-203 represses ‘stemness’ by repressing DeltaNp63. Cell Death Differ
Yi R et al (2008) A skin microRNA promotes differentiation by repressing ‘stemness’. Nature 452(7184):225–229
Manni I et al (2009) The microRNA miR-92 increases proliferation of myeloid cells and by targeting p63 modulates the abundance of its isoforms. FASEB J
Papagiannakopoulos T, Shapiro A, Kosik KS (2008) MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res 68(19):8164–8172
Liefer KM et al (2000) Down-regulation of p63 is required for epidermal UV-B-induced apoptosis. Cancer Res 60(15):4016–4020
Westfall MD et al (2005) Ultraviolet radiation induces phosphorylation and ubiquitin-mediated degradation of DeltaNp63alpha. Cell Cycle 4(5):710–716
Papoutsaki M et al (2005) A p38-dependent pathway regulates DeltaNp63 DNA binding to p53-dependent promoters in UV-induced apoptosis of keratinocytes. Oncogene 24(46):6970–6975
Chatterjee A et al (2010) Regulation of p53 Family Member Isoform Delta}Np63{alpha by the Nuclear Factor-{kappa}B Targeting Kinase I{kappa}B Kinase {beta}. Cancer Res 70(4):1419–1429
Fomenkov A et al (2004) RACK1 and stratifin target DeltaNp63alpha for a proteasome degradation in head and neck squamous cell carcinoma cells upon DNA damage. Cell Cycle 3(10):1285–1295
Lazzari C et al (2011) HIPK2 phosphorylates ΔNp63α and promotes its degradation in response to DNA damage. Oncogene 30(48):4802–4813
Rossi M et al (2006) The E3 ubiquitin ligase Itch controls the protein stability of p63. Proc Natl Acad Sci USA 103(34):12753–12758
Rossi M et al (2006) Itch/AIP4 associates with and promotes p63 protein degradation. Cell Cycle 5(16):1816–1822
Deutsch GB et al (2011) DNA damage in oocytes induces a switch of the quality control factor TAp63α from dimer to tetramer. Cell 144(4):566–576
Celli J et al (1999) Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome. Cell 99(2):143–153
McGrath JA et al (2001) Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of p63. Hum Mol Genet 10(3):221–229
Brunner HG, Hamel BCJ, van Bokhoven H (2002) P63 gene mutations and human developmental syndromes. Am J Med Genet 112(3):284–290
van Bokhoven H, McKeon F (2002) Mutations in the p53 homolog p63: allele-specific developmental syndromes in humans. Trends Mol Med 8(3):133–139
Rinne T et al (2006) Delineation of the ADULT syndrome phenotype due to arginine 298 mutations of the p63 gene. Eur J Hum Genet 14(8):904–910
Senoo M et al (2007) p63 Is essential for the proliferative potential of stem cells in stratified epithelia. Cell 129(3):523–536
Shalom-Feuerstein R et al (2010) ΔNp63 is an ectodermal gatekeeper of epidermal morphogenesis. Cell Death Differ
Candi E et al (2006) Differential roles of p63 isoforms in epidermal development: selective genetic complementation in p63 null mice. Cell Death Differ 13(6):1037–1047
Nguyen B-C et al (2006) Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation. Genes Dev 20(8):1028–1042
Wu G et al. ΔNp63α and tap63α regulate transcription of genes with distinct biological functions in cancer and development. Cancer Res
Su X et al (2009) TAp63 prevents premature aging by promoting adult stem cell maintenance. Cell Stem Cell 5(1):64–75
Katoh I et al (2000) p51A (TAp63gamma), a p53 homolog, accumulates in response to DNA damage for cell regulation. Oncogene 19(27):3126–3130
DeYoung MP et al (2006) Tumor-specific p73 up-regulation mediates p63 dependence in squamous cell carcinoma. Cancer Res 66(19):9362–9368
Truong AB et al (2006) p63 regulates proliferation and differentiation of developmentally mature keratinocytes. Genes Dev 20(22):3185–3197
Antonini D et al (2010) Transcriptional repression of miR-34 family contributes to p63-mediated cell cycle progression in epidermal cells. J Invest Dermatol 130(5):1249–1257
Keyes WM et al (2005) p63 deficiency activates a program of cellular senescence and leads to accelerated aging. Genes Dev 19(17):1986–1999
Guo X et al (2009) TAp63 induces senescence and suppresses tumorigenesis in vivo. Nat Cell Biol 11(12):1451–1457
Flores ER et al (2005) Tumor predisposition in mice mutant for p63 and p73: evidence for broader tumor suppressor functions for the p53 family. Cancer Cell 7(4):363–373
Keyes WM et al (2006) p63 heterozygous mutant mice are not prone to spontaneous or chemically induced tumors. Proc Natl Acad Sci USA 103(22):8435–8440
Hagiwara K et al (1999) Mutational analysis of the p63/p73L/p51/p40/CUSP/KET gene in human cancer cell lines using intronic primers. Cancer Res 59(17):4165–4169
Sunahara M et al (1999) Mutational analysis of p51A/TAp63gamma, a p53 homolog, in non-small cell lung cancer and breast cancer. Oncogene 18(25):3761–3765
Björkqvist AM et al (1998) DNA gains in 3q occur frequently in squamous cell carcinoma of the lung, but not in adenocarcinoma. Genes Chromosomes Canc 22(1):79–82
Hibi K et al (2000) AIS is an oncogene amplified in squamous cell carcinoma. Proc Natl Acad Sci USA 97(10):5462–5467
Massion PP et al (2003) Significance of p63 amplification and overexpression in lung cancer development and prognosis. Cancer Res 63(21):7113–7121
Sniezek JC et al (2004) Dominant negative p63 isoform expression in head and neck squamous cell carcinoma. Laryngoscope 114(12):2063–2072
Hu H et al (2002) Elevated expression of p63 protein in human esophageal squamous cell carcinomas. Int J Cancer 102(6):580–583
Wang TY et al (2001) Histologic and immunophenotypic classification of cervical carcinomas by expression of the p53 homologue p63: a study of 250 cases. Hum Pathol 32(5):479–486
Matos I et al (2005) p63, cytokeratin 5, and P-cadherin: three molecular markers to distinguish basal phenotype in breast carcinomas. Virchows Arch 447(4):688–694
Perou CM et al (2000) Molecular portraits of human breast tumours. Nature 406(6797):747–752
Leong C-O et al (2007) The p63/p73 network mediates chemosensitivity to cisplatin in a biologically defined subset of primary breast cancers. J Clin Invest 117(5):1370–1380
Ramsey MR et al (2011) Physical Association of HDAC1 and HDAC2 with p63 mediates transcriptional repression and tumor maintenance in squamous cell carcinoma. Cancer Res 71(13):4373–4379
Wu G et al (2005) DeltaNp63alpha up-regulates the Hsp70 gene in human cancer. Cancer Res 65(3):758–766
Keyes WM et al (2011) ΔNp63α is an oncogene that targets chromatin remodeler Lsh to drive skin stem cell proliferation and tumorigenesis. Cell Stem Cell 8(2):164–176
Pruneri G et al (2005) The transactivating isoforms of p63 are overexpressed in high-grade follicular lymphomas independent of the occurrence of p63 gene amplification. J Pathol 206(3):337–345
Quade BJ et al (2001) Expression of the p53 homologue p63 in early cervical neoplasia. Gynecol Oncol 80(1):24–29
Stefanou D et al (2004) p63 expression in benign and malignant breast lesions. Histol Histopathol 19(2):465–471
Wang X et al (2002) p63 expression in normal, hyperplastic and malignant breast tissues. Breast Cancer 9(3):216–219
Koga F et al (2003) Impaired p63 expression associates with poor prognosis and uroplakin III expression in invasive urothelial carcinoma of the bladder. Clin Cancer Res 9(15):5501–5507
Koga F et al (2003) Impaired Delta Np63 expression associates with reduced beta-catenin and aggressive phenotypes of urothelial neoplasms. Br J Cancer 88(5):740–747
Urist MJ et al (2002) Loss of p63 expression is associated with tumor progression in bladder cancer. Am J Pathol 161(4):1199–1206
Vanaja DK et al (2003) Transcriptional silencing of zinc finger protein 185 identified by expression profiling is associated with prostate cancer progression. Cancer Res 63(14):3877–3882
Haqq C et al (2005) The gene expression signatures of melanoma progression. Proc Natl Acad Sci USA 102(17):6092–6097
Su H et al (2003) Gene expression analysis of esophageal squamous cell carcinoma reveals consistent molecular profiles related to a family history of upper gastrointestinal cancer. Cancer Res 63(14):3872–3876
Su X et al (2010) TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. Nature 467(7318):986–990
Muller PAJ et al (2009) Mutant p53 drives invasion by promoting integrin recycling. Cell 139(7):1327–1341
Adorno M et al (2009) A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis. Cell 137(1):87–98
Fukushima H et al (2009) Loss of DeltaNp63alpha promotes invasion of urothelial carcinomas via N-cadherin/Src homology and collagen/extracellular signal-regulated kinase pathway. Cancer Res 69(24):9263–9270
Higashikawa K et al (2009) DeltaNp63alpha-dependent expression of Id-3 distinctively suppresses the invasiveness of human squamous cell carcinoma. Int J Cancer 124(12):2837–2844
Kommagani R et al (2009) Regulation of VDR by {Delta}Np63{alpha} is associated with inhibition of cell invasion. J Cell Sci
Ihrie RA et al (2005) Perp is a p63-regulated gene essential for epithelial integrity. Cell 120(6):843–856
Leonard MK et al (2011) ΔNp63α regulates keratinocyte proliferation by controlling PTEN expression and localization. Cell Death Differ
Girardini JE et al (2011) A Pin1/Mutant p53 axis promotes aggressiveness in breast cancer. Cancer Cell 20(1):79–91