Conflicting roles for p63 in skin development and carcinogenesis

Cell Cycle

Volumn 6, Issue 3, 2007, Pages 269-273

  Koster, Maranke I ^a   Dai, Sy ^a   Roop, Dennis R ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

Carcinogenesis; Differentiation; Epidermal; Epidermis; Keratinocyte; Morphogenesis; p63

Indexed keywords

PROTEIN P63;

ANIMAL EXPERIMENT; ANIMAL MODEL; CELL PROLIFERATION; CONTROLLED STUDY; DEHYDRATION; DNA BINDING; KERATINOCYTE; MORPHOGENESIS; MOUSE; NONHUMAN; PHENOTYPE; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; SKIN CARCINOGENESIS;

MUS;

EID: 33847054771     PISSN: 15384101     EISSN: 15514005     Source Type: Journal    
DOI: 10.4161/cc.6.3.3792     Document Type: Review

References (77)

1. Segre J. Complex redundancy to build a simple epidermal permeability barrier. Curr Opin Cell Biol 2003; 15:776-82.
2. Hardman MJ, Moore L, Ferguson MW, Byrne C. Barrier formation in the human fetus is patterned. J Invest Dermatol 1999; 113:1106-13.
3. Lechler T, Fuchs E. Asymmetric cell divisions promote stratification and differentiation of mammalian skin. Nature 2005; 437:275-80.
4. Smart IH. Variation in the plane of cell cleavage during the process of stratification in the mouse epidermis. Br J Dermatol 1970; 82:276-82.
5. Moll R, Franke WW, Schiller DL, Geiger B, Krepler R. The catalog of human cytokeratins: Patterns of expression in normal epithelia, tumors and cultured cells. Cell 1982; 31:11-24.
6. Byrne C, Tainsky M, Fuchs E. Programming gene expression in developing epidermis. Development 1994; 120:2369-83.
7. Nair M, Teng A, Bilanchone V, Agrawal A, Li B, Dai X. Ovol1 regulates the growth arrest of embryonic epidermal progenitor cells and represses c-myc transcription. J Cell Biol 2006; 173:253-64.
8. Sur I, Rozell B, Jaks V, Bergstrom A, Toftgard R. Epidermal and craniofacial defects in mice overexpressing Klf5 in the basal layer of the epidermis. J Cell Sci 2006; 119:3593-3601.
9. Koster MI, Kim S, Huang J, Williams T, Roop DR. TAp63α induces AP-2γ as an early event in epidermal morphogenesis. Dev Biol 2006; 289:253-61.
10. Dai X, Segre JA. Transcriptional control of epidermal specification and differentiation. Curr Opin Genet Dev 2004; 14:485-91.
11. Hu Y, Baud V, Delhase M, Zhang P, Deerinck T, Ellisman M, Johnson R, Karin M. Abnormal morphogenesis but intact IKK activation in mice lacking the IKKalpha subunit of IkappaB kinase. Science 1999; 284:316-20.
12. Takeda K, Takeuchi O, Tsujimura T, Itami S, Adachi O, Kawai T, Sanjo H, Yoshikawa K, Terada N, Akira S. Limb and skin abnormalities in mice lacking IKKalpha. Science 1999; 284:313-16.
13. Li Q, Lu Q, Hwang JY, Buscher D, Lee KF, Izpisua-Belmonte JC, Verma IM. IKK1-deficient mice exhibit abnormal development of skin and skeleton. Genes Dev 1999; 13:1322-28.
14. Ingraham CR, Kinoshita A, Kondo S, Yang B, Sajan S, Trout KJ, Malik MI, Dunnwald M, Goudy SL, Lovett M, Murray JC, Schutte BC. Abnormal skin, limb and craniofacial morphogenesis in mice deficient for interferon regulatory factor 6 (Irf6). Nat Genet 2006.
15. Richardson RJ, Dixon J, Malhotra S, Hardman MJ, Knowles L, Boot-Handford RP, Shore P, Whitmarsh A, Dixon MJ. Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch. Nat Genet 2006.
16. Herron BJ, Liddell RA, Parker A, Grant S, Kinne J, Fisher JK, Siracusa LD. A mutation in stratifin is responsible for the repeated epilation (Er) phenotype in mice. Nat Genet 2005; 37:1210-12.
17. Guenet JL, Salzgeber B, Tassin MT. Repeated epilation: A genetic epidermal syndrome in mice. J Hered 1979; 70:90-94.
18. Li Q, Lu Q, Estepa G, Verma IM. Identification of 14-3-3sigma mutation causing cutaneous abnormality in repeated-epilation mutant mouse. Proc Natl Acad Sci USA 2005; 102:15977-82.
19. Yang A, McKeon F. p63 and p73: p53 mimics, menaces and more. Nat Rev Mol Cell Biol 2000; 1:199-207.
20. Bourdon JC, Fernandes K, Murray-Zmijewski F, Liu G, Diot A, Xirodimas DP, Saville MK, Lane DP. p53 isoforms can regulate p53 transcriptional activity. Genes Dev 2005; 19:2122-37.
21. Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dotsch V, Andrews NC, Caput D, McKeon F. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing and dominant-negative activities. Mol Cell 1998; 2:305-16.
22. Koster MI, Kim S, Mills AA, DeMayo FJ, Roop DR. p63 is the molecular switch for initiation of an epithelial stratification program. Genes Dev 2004; 18:126-31.
23. King KE, Ponnamperuma RM, Yamashita T, Tokino T, Lee LA, Young MF, Weinberg WC. ΔNp63α functions as both a positive and a negative transcriptional regulator and blocks in vitro differentiation of murine keratinocytes. Oncogene 2003; 22:3635-44.
24. Ihrie RA, Marques MR, Nguyen BT, Horner JS, Papazoglu C, Bronson RT, Mills AA, Attardi LD. Perp is a p63-regulated gene essential for epithelial integrity. Cell 2005; 120:843-56.
25. Vigano MA, Lamartine J, Testoni B, Merico D, Alotto D, Castagnoli C, Robert A, Candi E, Melino G, Gidrol X, Mantovani R. New p63 targets in keratinocytes identified by a genome-wide approach. EMBO J 2006.
26. Westfall MD, Mays DJ, Sniezek JC, Pietenpol JA. The ΔNp63a 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 2003; 23:2264-76.
27. Barbieri CE, Perez CA, Johnson KN, Ely KA, Billheimer D, Pietenpol JA. IGFBP-3 is adirect target of transcriptional regulation by ΔNp63a in squamous epithelium. Cancer Res 2005; 65:2314-20.
28. Nguyen BC, Lefort K, Mandinova A, Antonini D, Devgan V, Della GG, Koster MI, Zhang Z, Wang J, Tommasi d, V, Kitajewski J, Chiorino G, Roop DR, Missero C, Dotto GP. Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation. Genes Dev 2006; 20:1028-42.
29. Thanos CD, Bowie JU. p53 family members p63 and p73 are SAM domain-containing proteins. Protein Sci 1999; 8:1708-10.
30. Siegfried E, Bree A, Fete M, Sybert VP. Skin erosions and wound healing in ankyloblepharon-ectodermal defect-cleft lip and/or palate. Arch Dermatol 2005; 141:1591-94.
31. 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. Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of p63. Hum Mol Genet 2001; 10:221-29.
32. Bakkers J, Hild M, Kramer C, Furutani-Seiki M, Hammerschmidt M. Zebrafish ΔNp63 is a direct target of Bmp signaling and encodes a transcriptional repressor blocking neural specification in the ventral ectoderm. Dev Cell 2002; 2:617-27.
33. Antonini D, Rossi B, Han R, Minichiello A, Di Palma T, Corrado M, Banfi S, Zannini M, Brissette JL, Missero C. An autoregulatory loop directs the tissue-specific expression of p63 through a long-range evolutionarily conserved enhancer. Mol Cell Biol 2006; 26:3308-18.
34. Romano RA, Birkaya B, Sinha S. Defining the regulatory elements in the proximal promoter of ΔNp63 in keratinocytes: Potential roles for Sp1//Sp3, NF-Y and p63. J Invest Dermatol 2006; 126:1469-79.
35. Ghioni P, D'Alessandra Y, Mansueto G, Jaffray E, Hay RT, Mantia GL, Guerrini L. The protein stability and transcriptional activity of p63alpha are regulated by SUMO-1 conjugation. Cell Cycle 2005; 4.
36. Papoutsaki M, Moretti F, Lanza M, Marinari B, Sartorelli V, Guerrini L, Chimenti S, Levrero M, Costanzo A. A p38-dependent pathway regulates ΔNp63 DNA binding to p53-dependent promoters in UV-induced apoptosis of keratinocytes. Oncogene 2005; 24:6970-75.
37. Huang YP, Wu G, Guo Z, Osada M, Fomenkov T, Park HL, Trink B, Sidransky D, Fomenkov A, Ratovitski EA. Altered sumoylation of p63a contributes to the split-hand/foot malformation phenotype. Cell Cycle 2004; 3:1587-96.
38. Westfall MD, Joyner AS, Barbieri CE, Livingstone M, Pietenpol JA. Ultraviolet radiation induces phosphorylation and ubiquitin-mediated degradation of ΔNp63a. Cell Cycle 2005; 4:710-16.
39. Rossi M, Aqeilan RI, Neale M, Candi E, Salomoni P, Knight RA, Croce CM, Melino G. The E3 ubiquitin ligase Itch controls the protein stability of p63. Proc Natl Acad Sci USA 2006; 103:12753-58.
40. Rossi M, De SM, Pollice A, Santoro R, La MG, Guerrini L, Calabro V. Itch/AIP4 associates with and promotes p63 protein degradation. Cell Cycle 2006; 5:1816-22.
41. Mills AA. p63: Oncogene or tumor suppressor? Curr Opin Genet Dev 2006; 16:38-44.
42. McKeon F. p63 and the epithelial stem cell: More than status quo? Genes Dev 2005; 18:465-69.
43. Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson RT, Tabin C, Sharpe A, Caput D, Crum C, McKeon F. p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature 1999; 398:714-18.
44. Mills AA, Zheng B, Wang XJ, Vogel H, Roop DR, Bradley A. p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature 1999; 398:708-13.
45. Pellegrini G, Dellambra E, Golisano O, Martinelli E, Fantozzi I, Bondanza S, Ponzin D, McKeon F, De Luca M. p63 identifies keratinocyte stem cells. Proc Natl Acad Sci USA 2001; 98:3156-61.
46. Liefer KM, Koster MI, Wang XJ, Yang A, McKeon F, Roop DR. Down-regulation of p63 is required for epidermal UV-B-induced apoptosis. Cancer Res 2000; 60:4016-20.
47. Keyes WM, Wu Y, Vogel H, Guo X, Lowe SW, Mills AA. p63 deficiency activates a program of cellular senescence and leads to accelerated aging. Genes Dev 2005; 19:1986-99.
48. Nylander K, Vojtesek B, Nenutil R, Lindgren B, Roos G, Zhanxiang W, Sjostrom B, Dahlqvist A, Coates PJ. Differential expression of p63 isoforms in normal tissues and neoplastic cells. J Pathol 2002; 198:417-427.
49. Parsa R, Yang A, McKeon F, Green H. Association of p63 with proliferative potential in normal and neoplastic human keratinocytes. J Invest Dermatol 1999; 113:1099-1105.
50. Ohyama M, Terunuma A, Tock CL, Radonovich MF, Pise-Masison CA, Hopping SB, Brady JN, Udey MC, Vogel JC. Characterization and isolation of stem cell-enriched human hair follicle bulge cells. J Clin Invest 2006; 116:249-60.
51. Larderet G, Fortunel NO, Vaigot P, Cegalerba M, Maltere P, Zobiri O, Gidrol X, Waksman G, Martin MT. Human side population keratinocytes exhibit long-term proliferative potential and a specific gene expression profile and can form a pluristratified epidermis. Stem Cells 2006; 24:965-74.
52. Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M, Fuchs E. Defining the epithelial stem cell niche in skin. Science 2005; 303:359-63.
53. Morris RJ, Liu Y, Marles L, Yang Z, Trempus C, Li S, Lin JS, Sawicki JA, Cotsarelis G. Capturing and profiling adult hair follicle stem cells. Nat Biotechnol 2004; 22:411-17.
54. Candi E, Rufini A, Terrinoni A, Dinsdale D, Ranalli M, Paradisi A, De Laurenzi V, Spagnoli LG, Catani MV, Ramadan S, Knight RA, Melino G. Differential roles of p63 isoforms in epidermal development: Selective genetic complementation in p63 null mice. Cell Death Differ 2006; 13:1037-47.
55. Laurikkala J, Mikkola ML, James M, Tummers M, Mills AA, Thesleff I. p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation. Development 2006; 133:1553-63.
56. Thorey IS, Meneses JJ, Neznanov N, Kulesh DA, Pedersen RA, Oshima RG. Embryonic expression of human keratin 18 and K18-β-galactosidase fusion genes in transgenic mice. Dev Biol 1993; 160:519-34.
57. Koster MI, Lu SL, White LD, Wang XJ, Roop DR. Reactivation of developmentally expressed p63 isoforms predisposes to tumor development and progression. Cancer Res 2006; 66:3981-86.
58. King KE, Ponnamperuma RM, Gerdes MJ, Tokino T, Yamashita T, Baker CC, Weinberg WC. Unique domain functions of p63 isotypes that differentially regulate distinct aspects of epidermal homeostasis. Carcinogenesis 2006; 27:53-63.
59. Bamberger C, Pollet D, Schmale H. Retinoic acid inhibits downregulation of Np63a expression during terminal differentiation of human primary keratinocytes. J Invest Dermatol 2002; 118:133-38.
60. Ellisen LW, Ramsayer KD, Johannessen CM, Yang A, Beppu H, Minda K, Oliner JD, McKeon F, Haber DA. REDD1, a developmentally regulated transcriptional target of p63 and p53, links p63 to regulation of reactive oxygen species. Mol Cell 2002; 10:995-1005.
61. Wu G, Osada M, Guo Z, Fomenkov A, Begum S, Zhao M, Upadhyay S, Xing M, Wu F, Moon C, Westra WH, Koch WM, Mantovani R, Califano JA, Ratovitski E, Sidransky D, Trink B. Np63a up-regulates the Hsp70 gene in human cancer. Cancer Res 2005; 65:758-66.
62. Sbisa E, Mastropasqua G, Lefkimmiatis K, Caratozzolo MF, D'Erchia AM, Tullo A. Connecting p63 to cellular proliferation: The example of the adenosine deaminase target gene. Cell Cycle 2006; 5:205-12.
63. Missero C, Calautti E, Eckner R, Chin J, Tsai LH, Livingston DM, Dotto GP. Involvement of the cell-cycle inhibitor Cip1/WAF1 and the E1A-associated p300 protein in terminal differentiation. Proc Natl Acad Sci USA 1995; 92:5451-55.
64. Rangarajan A, Talora C, Okuyama R, Nicolas M, Mammucari C, Oh H, Aster JC, Krishna S, Metzger D, Chambon P, Miele L, Aguet M, Radtke F, Dotto GP. Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation. EMBO J 2001; 20:3427-36.
65. Beretta C, Chiarelli A, Testoni B, Mantovani R, Guerrini L. Regulation of the cyclin-dependent kinase inhibitor p57Kip2 expression by p63. Cell Cycle 2005; 4:1625-31.
66. Martinez LA, Chen Y, Fischer SM, Conti CJ. Coordinated changes in cell cycle machinery occur during keratinocyte terminal differentiation. Oncogene 1999; 18:397-406.
67. Testoni B, Mantovani R. Mechanisms of transcriptional repression of cell-cycle G2/M promoters by p63. Nucleic Acids Res 2006; 34:928-38.
68. Flores ER, Sengupta S, Miller JB, Newman JJ, Bronson R, Crowley D, Yang A, McKeon F, Jacks T. Tumor predisposition in mice mutant for p63 and p73: Evidence for broader tumor suppressor functions for the p53 family. Cancer Cell 2005; 7:363-73.
69. Ikawa S, Nakagawara A, Ikawa Y. p53 family genes: Structural comparison, expression and mutation. Cell Death Differ 1999; 6:1154-61.
70. Osada M, Ohba M, Kawahara C, Ishioka C, Kanamaru R, Katoh I, Ikawa Y, Nimura Y, Nakagawara A, Obinata M, Ikawa S. Cloning and functional analysis of human p51, which structurally and functionally resembles p53. Nat Med 1998; 4:839-43.
71. Sunahara M, Shishikura T, Takahashi M, Todo S, Yamamoto N, Kimura H, Kato S, Ishioka C, Ikawa S, Ikawa Y, Nakagawara A. Mutational analysis of p51A/TAp63gamma, a p53 homolog, in non-small cell lung cancer and breast cancer. Oncogene 1999; 18:3761-65.
72. Park BJ, Lee SJ, Kim JI, Lee SJ, Lee CH, Chang SG, Park JH, Chi SG. Frequent alteration of p63 expression in human primary bladder carcinomas. Cancer Res 2000; 60:3370-74.
73. Koga F, Kawakami S, Fujii Y, Saito K, Ohtsuka Y, Iwai A, Ando N, Takizawa T, Kageyama Y, Kihara K. Impaired p63 expression associates with poor prognosis and uroplakin III expression in invasive urothelial carcinoma of the bladder. Clin Cancer Res 2003; 9:5501-07.
74. Urist MJ, Di Como CJ, Lu ML, Charytonowicz E, Verbel D, Crum CP, Ince TA, McKeon FD, Cordon-Cardo C. Loss of p63 expression is associated with tumor progression in bladder cancer. Am J Pathol 2002; 161:1199-1206.
75. Mills AA. p63: Oncogene or tumor suppressor? Curr Opin Genet Dev 2006; 16:38-44.
76. Keyes WM, Vogel H, Koster MI, Guo X, Qi Y, Petherbridge KM, Lowe SW, Roop DR, Bradley A, Mills AA. p63 heterozygous mutant mice are not tumor prone. Cancer Res submitted (2005).
77. Perez-Losada J, Wu D, Delrosario R, Balmain A, Mao JH. p63 and p73 do not contribute to p53-mediated lymphoma suppressor activity in vivo. Oncogene 2005; 24:5521-24.