Abstract
The presented data indicate that the p63 gene is required for the commitment of epidermal stem cells in embryonic development. At the same time, p63 underlies many functions involved in the self-renewal of stem cells in the adult epidermis. Its expression provides for keratinocyte adhesion, inhibits apoptosis, and maintains the integrity of the epidermal tissue.
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Byrne, C., Tainsky, M., and Fuchs, E., Programming Gene Expression in Developing Epidermis, Development, 1994, vol. 120, pp. 2369–2383.
Carroll, D.K., Carroll, J.S., Leong, C.-O., et al., P63 Regulates an Adhesion Programme and Cell Survival in Epithelial Cells, Nature Cell Biol., 2006, vol. 8, pp. 551–561.
Celli, J., Duijf, P., Hamel, B.C., et al., Heterozygous Germline Mutations in the p53 Homologue p63 Are the Cause of EEC Syndrome, Cell, 1999, vol. 99, pp. 143–153.
Di Iorio, E., Barbaro, V., Ruzza, A., et al., Isoforms of ΔNp63 and the Migration of Ocular Limbal Cells in Human Corneal Regeneration, Proc. Natl. Acad. Sci. USA, 2005, vol. 102, pp. 9523–9528.
Flores, E.R., Tsai, K.Y., Crowley, D., et al., P63 and p73 Are Required for p53 Dependent Apoptosis in Response to DNA Damage, Nature, 2002, vol. 416, pp. 560–564.
Frisch, S.M. and Francis, H., Disruption of Epithelial Cell-Matrix Interactions Induces Apoptosis, J. Cell Biol., 1994, vol. 124, pp. 619–626.
Ghazizadeh, S. and Taichman, L.B., Organization of Stem Cells and Their Progeny in Human Epidermis, J. Invest. Dermatol., 2005, vol. 124, pp. 367–372.
Ihrie, R.A., Marques, M.R., Nguyen, B.T., et al., Perp is a p63-Regulated Gene Essential for Epithelial Integrity, Cell, 2005, vol. 120, pp. 843–856.
Jackson, B.W., Grund, C., Winter, S., et al., Formation of Cytoskeletal Elements during Mouse Embryogenesis. II. Epithelial Differentiation and Intermediate-Sized Filaments in Early Postimplantation Embryos, Differentiation, 1981, vol. 20, pp. 203–216.
Jones, P.H. and Watt, F.M., Separation of Human Epidermal Stem Cells from Transit Amplifying Cells on the Basis of Differences in Integrin Function and Expression, Cell, 1993, vol. 73, pp. 713–724.
Jones, P.H., Harper, S., and Watt, F.M., Stem Cell Patterning and Fate in Human Epidermis, Cell, 1995, vol. 80, pp. 83–93.
Kaur, P. and Li, A., Adhesive Properties of Human Basal Epidermal Cells: An Analysis of Keratinocyte Stem Cells, Transit Amplifying Cells, and Postmitotic Differentiating Cells, J. Invest. Dermatol., 2000, vol. 114, pp. 413–420.
Keyes, W.M., Wu, Y., Vogel, H., et al., P63 Deficiency Activates a Program of Cellular Senescence and Leads to Accelerated Aging, Genes Development, 2005, vol. 9, pp. 1986–1999.
King, K.E., Ponnamperuma, R.M., Yamashita, T., et al., ΔNp63α Functions as Both a Positive and a Negative Transcriptional Regulator and Blocks in Vitro Differentiation of Murine Keratinocytes, Oncogene, 2003, vol. 22, pp. 3635–3644.
Koster, M.I. and Roop, D.R., The Role of p63 in Development and Differentiation of the Epidermis, J. Dermatol. Sci., 2004, vol. 34, pp. 3–9.
Koster, M.I., Kim, S., Mills, A.A., et al., P63 Is the Molecular Switch for Initiation of an Epithelial Stratification Program, Genes Dev., 2004, vol. 18, pp. 126–131.
Kurata, S.-I., Okuyama, T., Osada, M., et al., P51/p63 Controls Subunit α3 of the Major Epidermis Integrin Anchoring the Stem Cells to the Niche, J. Biol. Chem., 2004, vol. 279, pp. 50069–50077.
Lohrum, M.A.E. and Vousden, K.H., Regulation and Function of the p53-Related Proteins: Same Family, Different Rules, Trends Cell Biol., 2000, vol. 10, pp. 197–202.
Mills, A.A., Zheng, B.H., Wang, X.J., et al., P63 Is a p53 Homologue Required for Limb and Epidermal Morphogenesis, Nature, 1999, vol. 398, pp. 708–713.
Moll, R., Franke, W.W., Schiller, D.L., et al., The Catalog of Human Cytokeratins: Patterns of Expression in Normal Epithelia, Tumors and Cultured Cells, Cell, 1982, vol. 31, pp. 11–24.
Noszczyk, B.H. and Majewski, S.T., P63 Expression during Normal Cutaneous Wound Healing in Humans, Plast. Reconstr. Surg., 2001, vol. 108, pp. 1242–1247.
Parsa, R., Yang, A., McKeon, F., and Green, H., Association of p63 with Proliferative Potential in Normal and Neoplastic Human Keratinocytes, J. Invest. Dermatol., 1999, vol. 113, pp. 1099–1105.
Pellegrini, G., Dellambra, E., Golisano, O., et al., P63 Identifies Keratinocytes Stem Cells, Proc. Nat. Acad. Sci. USA, 2001, vol. 98, pp. 3156–3161.
Radu, E., Simionescu, O., Regalia, T., et al., Stem Cells (p63+) in Keratinocyte Cultures from Human Adult Skin, J. Cell Mol. Med, 2002, vol. 6, pp. 593–598.
Tiberio, R., Marconi, A., Fila, C., et al., Keratinocytes Enriched for Stem Cells Are Protected from Anoikis via an Integrin Signaling Pathway in a Bcl-2 Dependent Manner, FEBS Lett., 2002, vol. 524, pp. 139–144.
Tsujita-Kyutoku, M., Kiuchi, K., Danbara, N., et al., P63 Expression in Normal Human Epidermis and Epidermal Appendages and Their Tumors, J. Cutan. Pathol., 2003, vol. 30, pp. 11–17.
Vorotelyak, E.A., Chermnykh, E.S., Vasiliev, A.V., et al., Heterogeneity and Structural Arrangement of Human Keratinocytes in Vitro, J. Investing. Dermatol., 2005, vol. 124, p. A60.
Westfall, M.D. and Pietenpol, J.A., P63: Molecular Complexity in Development and Cancer, Carcinogenesis, 2004, vol. 25, pp. 857–864.
Wu, G., Nomoto, S., Hogue, M.O., et al., ΔNp63α and TAp63α Regulate Transcription of Genes with Distinct Biological Functions in Cancer and Development, Cancer Res., 2003, vol. 63, pp. 2351–2357.
Yang, A. and McKeon, F., P63 and p73: p53 Mimics, Menaces and More, Nature Rev. Molec. Cell Biol., 2000, vol. 1, pp. 199–207.
Yang, A., Kaghad, M., Wang, Y., et al., P63, a p53 Homolog at 3q27-29, Encodes Multiple Products with Transactivating, Death-Inducing, and Dominant-Negative Activities, Mol. Cell, 1998, vol. 2, pp. 305–316.
Yang, A., Schweitzer, R., Sun, D., et al., P63 Is Essential for Regenerative Proliferation in Limb, Craniofacial and Epithelial Development, Nature, 1999, vol. 398, pp. 714–718.
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Original Russian Text © E.A. Vorotelyak, E.S. Chermnykh, S.B. Tkachenko, A.V. Vasiliev, V.V. Terskikh, 2007, published in Izvestiya Akademii Nauk, Seriya Biologicheskaya, 2007, No. 4, pp. 389–393.
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Vorotelyak, E.A., Chermnykh, E.S., Tkachenko, S.B. et al. Expression and function of p63 gene in epithelial cells. Biol Bull Russ Acad Sci 34, 319–322 (2007). https://doi.org/10.1134/S1062359007040012
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DOI: https://doi.org/10.1134/S1062359007040012