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The p53 Gene Family: Control of Cell Proliferation and Developmental Programs

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Abstract

For a quarter of a century the gene p53 has attracted close attention of scientists who deal with problems of carcinogenesis and maintenance of genetic stability. Multicellular organisms on our planet owe their rich evolution in many respects to the ability of this gene to protect cells from oncogenic transformation and harmful changes in DNA. A relatively recent discovery of structural p53 homologs, the genes p63 and p73, which seem to have more ancient roots, has roused keen interest in their function. Do they carry out oncosuppressor functions in partnership with p53 or do they possess their own specific functions? This review analyzes data on p53, p63, and p73 functional activity at the levels of the molecule, cell, and whole organism with the accent on examination of specific p63/p73 targets indicating a unique role of these genes in control of developmental processes.

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REFERENCES

  1. Futreal, P. A., Kasprzyk, A., Birnney, E., Mullikin, J. C., Wooster, R., and Stratton, M. R. (2001) Nature, 409, 850–855.

    Article  PubMed  Google Scholar 

  2. Giaccia, A. J., and Kastan, M. B. (1998) Genes Dev., 12, 2973–2983.

    PubMed  Google Scholar 

  3. Derry, W. B., Putzke, A. P., and Rothman, J. H. (2001) Science, 294, 591–595.

    Article  PubMed  Google Scholar 

  4. Ollmann, M., Young, L. M., Como, C. J., Karim, F., Belvin, M., Robertson, S., Whittaker, K., Demsky, M., Fisher, W. W., Buchman, A., Duyk, G., Friedman, L., Prives, C., and Kopczynski, C. (2000) Cell, 101, 91–101.

    Article  PubMed  Google Scholar 

  5. Yang, A., Kaghad, M., Wang, Y., Gillett, E., Fleming, M. D., Dotsch, V., Andrews, N. C., Caput, D., and McKeon, F. (1998) Mol. Cell., 2, 305–316.

    Article  PubMed  Google Scholar 

  6. Little, N. A., and Jochemsen, A. G. (2002) IJBCB, 34, 6–9.

    Google Scholar 

  7. Kaghad, M., Bonnet, H., Yang, A., Creancier, L., Biscan, J. C., Valent, A., Minty, A., Chalon, P., Lelias, J.-M., Dumont, X., Ferrara, P., McKeon, F., and Caput, D. (1997) Cell, 90, 809–819.

    Article  PubMed  Google Scholar 

  8. Yang, A., Kaghad, M., Caput, D., and McKeon, F. (2002) Trends Genet., 18, 90–95.

    Article  PubMed  Google Scholar 

  9. Irwin, M. S., and Kaelin, W. G. (2001) Cell Growth Differ., 12, 337–349.

    PubMed  Google Scholar 

  10. Thanos, C. D., and Bowie, J. U. (1999) Protein Sci., 8, 1708–1710.

    PubMed  Google Scholar 

  11. Schultz, J., Ponting, C. P., Hofmann, K., and Bork, P. (1997) Protein Sci., 6, 249–253.

    PubMed  Google Scholar 

  12. Ghioni, P., Bolognese, F., Duijf, P. H. G., Bokhoven, H., Mantovani, R., and Guerrini, L. (2002) Mol. Cell. Biol., 22, 8659–8668.

    Article  PubMed  Google Scholar 

  13. Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A., Jr., Butel, J. S., and Bradley, A. (1992) Nature, 356, 215–221.

    Article  PubMed  Google Scholar 

  14. Mills, A. A., Zheng, B., Wang, X., Vogel, H., Roop, D. R., and Bradley, A. (1999) Nature, 398, 708–713.

    Article  PubMed  Google Scholar 

  15. Yang, A., Schweitzer, R., Sun, D., Kaghad, M., Walker, N., Bronson, R. T., Tabin, C., Sharpe, A., Caput, D., Crum, C., and McKeon, F. (1999) Nature, 398, 714–718.

    Article  PubMed  Google Scholar 

  16. Celli, J., Duijf, P., Hamel, B. C. J., Bamshad, M., Kramer, B., Smits, A. P. T., Newbury-Ecob, R., Hennekam, R. C. M., Buggenhout, G. V., Haeringen, A., Woods, C. G., Essen, A. J., Waal, R., Vriend, G., Haber, D. A., Yang, A., McKeon, F., Brunner, H. G., and Bokhoven, H. (1999) Cell, 99, 143–153.

    Article  PubMed  Google Scholar 

  17. McGrath, J. A., Duijf, P. H., Doetsch, V., Irvine, A. D., Waal, R., Vanmolkot, K. R., Wessagowit, V., Kelly, A., Atherton, D. J., Griffiths, W. A., Orlow, S. J., van Haeringen, A., Ausems, M. G., Yang, A., McKeon, F., Bamshad, M. A., Brunner, H. G., Hamel, B. C., and Bokhoven, H. (2001) Hum. Mol. Genet., 10, 221–229.

    Article  PubMed  Google Scholar 

  18. Yang, A., Walker, N., Bronson, R., Kaghad, M., Oosterwegel, M., Bonnin, J., Vagner, C., Bonnet, H., Dikker, P., Sharpe, A., McKeon, F., and Caput, D. (2000) Nature, 404, 99–102.

    Article  PubMed  Google Scholar 

  19. Chumakov, P. M. (2000) Biochemistry (Moscow), 65, 28–40.

    Google Scholar 

  20. May, P., and May, E. (1999) Oncogene, 18, 7621–7636.

    Article  PubMed  Google Scholar 

  21. Michael, D., and Oren, M. (2002) Curr. Opin. Genet. Dev., 12, 53–59.

    Article  PubMed  Google Scholar 

  22. Ashcroft, M., and Vousden, K. H. (1999) Oncogene, 18, 7637–7643.

    Article  PubMed  Google Scholar 

  23. Ryan, K. M., Phillips, A. C., and Vousden, K. H. (2001) Curr. Opin. Cell Biol., 13, 332–337.

    Article  PubMed  Google Scholar 

  24. El-Deiry, W. S., Kern, S. E., Pitenpol, J. A., Kinzler, K. W., and Vogelstein, B. (1992) Nat. Genet., 1, 45–49.

    Article  PubMed  Google Scholar 

  25. Cho, Y. J., Gorina, S., Jeffrey, P. D., and Pavletich, N. P. (1994) Science, 256, 346–355.

    Google Scholar 

  26. Sigal, A., and Rotter, V. (2000) Cancer Res., 60, 6788–6793.

    PubMed  Google Scholar 

  27. Kopnin, B. P. (2000) Biochemistry (Moscow), 65, 2–27.

    Google Scholar 

  28. Dragovich, T., Rudin, C. M., and Thompson, C. B. (1998) Oncogene, 17, 3207–3213.

    Article  PubMed  Google Scholar 

  29. Schuler, M., and Green, D. R. (2001) Biochem. Soc. Trans., 29, 684–688.

    Article  PubMed  Google Scholar 

  30. Ding, Y., Inoue, T., Kamiyama, A. J., Tamura, Y., Ohtani-Fujita, N., Igata, E., and Sakai, T. (1999) DNA Res., 6, 347–351.

    Article  PubMed  Google Scholar 

  31. Strano, S., Rossi, M., Fontemaggi, G., Munarriz, E., Soddu, S., Sacchi, A., and Blandino, G. (2001) FEBS Lett., 490, 163–170.

    Article  PubMed  Google Scholar 

  32. Ishimoto, O., Kawahara, C., Enjo, K., Obinata, M., Nukiwa, T., and Ikawa, S. (2002) Cancer Res., 62, 636–641.

    PubMed  Google Scholar 

  33. Irwin, M. S., and Kaelin, W. G., Jr. (2001) Apoptosis, 6, 17–29.

    Article  PubMed  Google Scholar 

  34. Benard, J., Douc-Rasy, S., and Ahomadegbe, J. C. (2003) Hum. Mutat., 21, 182–191.

    Article  PubMed  Google Scholar 

  35. Nakagawa, T., Takahashi, M., Ozaki, T., Watanabe, K., Todo, S., Mizuguchi, H., Hayakawa, T., and Nakagawara, A. (2002) Mol. Cell. Biol., 22, 2575–2585.

    Article  PubMed  Google Scholar 

  36. Levrero, M., Laurenzi, V., Cotanzo, A., Sabatini, S., Gong, J., Wang, J. Y. J., and Melino, G. (2000) J. Cell Sci., 113, 1661–1670.

    PubMed  Google Scholar 

  37. Pozniak, C. D., Radinovic, S., Yang, A., McKeon, F., Kaplan, D. R., and Miller, F. D. (2000) Science, 289, 304–306.

    Article  PubMed  Google Scholar 

  38. Laurenzi, V., Raschella, G., Barcaroli, D., Annicchiarico-Petruzzelli, M., Ranalli, M., Catani, M. V., Tanno, B., Costanzo, A., Levrero, M., and Melino, G. (2000) J. Biol. Chem., 275, 15226–15231.

    Article  PubMed  Google Scholar 

  39. Kerszberg, M. (1999) Semin. Cell Dev. Biol., 10, 297–302.

    Article  PubMed  Google Scholar 

  40. Tabata, T., and Takei, Y. (2004) Development, 131, 703–712.

    Article  PubMed  Google Scholar 

  41. Maden, M., and Hind, M. (2003) Dev. Dynamics, 226, 237–244.

    Article  Google Scholar 

  42. Parsa, R., Yang, A., McKeon, F., and Green, H. (1999) J. Invest. Dermatol., 113, 1099–1105.

    Article  PubMed  Google Scholar 

  43. Bamberger, C., Pollet, D., and Schmale, H. (2002) J. Invest. Dermatol., 118, 133–138.

    Article  PubMed  Google Scholar 

  44. Maden, M. (2002) Int. J. Dev. Biol., 46, 883–886.

    PubMed  Google Scholar 

  45. Yashiro, K., Zhao, X., Uehara, M., Yamashita, K., Nishijima, M., Nishino, J., Saijoh, Y., Sakai, Y., and Hamada, H. (2004) Dev. Cell, 6, 411–422.

    Article  PubMed  Google Scholar 

  46. Morriss-Kay, G. M., and Ward, S. J. (1999) Int. Rev. Cytol., 188, 73–31.

    PubMed  Google Scholar 

  47. Odelberg, S. J., Kollhoff, A., and Keating, M. T. (2000) Cell, 103, 1099–1109.

    Article  PubMed  Google Scholar 

  48. Stocum, D. L. (2004) Curr. Top. Microbiol. Immunol., 280, 1–70.

    PubMed  Google Scholar 

  49. Ishibashi, K., Sasaki, S., Fushimi, K., Uchida, S., Kuwahara, M., Saito, H., Furukawa, T., Nakajima, K., Yamaguchi, Y., Gojobori, T., and Marumo, F. (1994) Proc. Natl. Acad. Sci. USA, 91, 6269–6273.

    PubMed  Google Scholar 

  50. Zheng, X., and Chen, X. (2001) FEBS Lett., 489, 4–7.

    Article  PubMed  Google Scholar 

  51. Zheng, X., and Bollinger, B. W. (2003) J. Invest. Dermatol., 121, 1487–1495.

    Article  PubMed  Google Scholar 

  52. Fontemaggi, G., Kele, I., Amariglio, N., Rechavi, G., Krishnamurthy, J., Strano, S., Sacchi, A., Givol, D., and Blandino, G. (2002) J. Biol. Chem., 277, 43359–43368.

    Article  PubMed  Google Scholar 

  53. Morgan, K., and Kalsheker N. A. (1997) IJBCB, 29, 1501–1511.

    Google Scholar 

  54. Janciauskiene, S. (2001) Biochim. Biophys. Acta, 1535, 221–235.

    PubMed  Google Scholar 

  55. Sunderman, F. W., Jr., Varghese, A. H., Kroftova, O. S., Grbac-Ivankovic, S., Kotyza, J., Datta, A. K., Davis, M., Bal, W., and Kasprzak, K. S. (1996) Reprod. Dev., 44, 507–524.

    Article  Google Scholar 

  56. Kawamura, K., Hayata, D., Fujiwara, S., and Yubisui, T. (1998) J. Biochem. (Tokyo), 124, 1004–1012.

    Google Scholar 

  57. Gao, F., Shi, H. Y., Daughty, C., Cella, N., and Zhang, M. (2004) Development, 131, 1479–1489.

    Article  PubMed  Google Scholar 

  58. Xia, L., Stoll, S. W., Liebert, M., Ethier, S. P., Carey, T., Esclamado, R., Carroll, W., Johnson, T. M., and Elder J. T. (1997) Cancer Res., 57, 3055–3062.

    PubMed  Google Scholar 

  59. Feng, G., Xu, X., Youssef, E. M., and Lotan, R. (2001) Cancer Res., 61, 7999–8004.

    PubMed  Google Scholar 

  60. Hibi, K., Fujitake, S., Takase, T., Kodera, Y., Ito, K., Akiyama, S., Shirane, M., and Nakao, A. (2003) Clin. Cancer Res., 9, 4282–4285.

    PubMed  Google Scholar 

  61. Artavanis-Tsakonas, S., Rand, M. D., and Lake, R. J. (1999) Science, 284, 770–776.

    Article  PubMed  Google Scholar 

  62. Greenwald, I. (1998) Genes Dev., 12, 1751–1762.

    PubMed  Google Scholar 

  63. Freemantle, S. J., Kerley, J. S., Olsen, S. L., Gross, R. H., and Spinella, M. J. (2002) Oncogene, 21, 2880–2889.

    Article  PubMed  Google Scholar 

  64. Raya, A., Kawakami, Y., Rodriguez-Esteban, C., Ibanes, M., Rasskin-Gutman, D., Rodriguez-Leon, J., Buscher, D., Feijo, J. A., and Izpisua-Belmonte, J. C. (2004) Nature, 427, 121–128.

    Article  PubMed  Google Scholar 

  65. Freitas, C., Rodrigues, S., Charrier, J. B., Teillet, M. A., and Palmeirim, I. (2001) Development, 128, 5139–5147.

    PubMed  Google Scholar 

  66. Li, L., Krantz, I. D., Deng, Y., Genin, A., Banta, A. B., Collins, C. C., Qi, M., Trask, B. J., Kuo, W. L., Cochran, J., Costa, T., Pierpont, M. E., Rand, E. B., Piccoli, D. A., Hood, L., and Spinner, N. B. (1997) Nat. Genet., 16, 243–251.

    Article  PubMed  Google Scholar 

  67. Sasaki, Y., Ishida, S., Morimoto, I., Yamashita, T., Kojima, T., Kihara, C., Tanaka, T., Imai, K., Nakamura, Y., and Tokino, T. (2002) J. Biol. Chem., 277, 719–724.

    Article  PubMed  Google Scholar 

  68. Laurenzi, V., Rossi, A., Terrinoni, A., Barcaroli, D., Levrero, M., Costanzo, A., Knight, R. A., Guerrieri, P., and Melino, G. (2000) Biochem. Biophys. Res. Commun., 273, 342–346.

    Article  PubMed  Google Scholar 

  69. Wu, G., Nomoto, S., Hoque, M. O., Dracheva, T., Osada, M., Lee, C. R., Dong, S. M., Guo, Z., Benoi, N., Cohen, Y., Rechthand, P., Califano, J., Moon, C., Ratovitski, E., Jen, J., Sidransky, D., and Trink, B. (2003) Cancer Res., 63, 2351–2357.

    PubMed  Google Scholar 

  70. Zhang, W., and Chen, H. (2002) Sheng Wu Yi Xue Gong Cheng Xue Za Zhi., 19, 697–702.

    PubMed  Google Scholar 

  71. Xie, K. (2001) Cytokine Growth Factor Rev., 12, 375–391.

    Article  PubMed  Google Scholar 

  72. Damme, J., Rampart, M., Conings, R., Decock, B., Osselaer, N., Willems, J., and Billiau, A. (1990) Eur. J. Immunol., 20, 2113–2118.

    PubMed  Google Scholar 

  73. Resmi, K. R., and Krishnan, L. K. (2002) Thromb. Res., 106, 229–236.

    Article  PubMed  Google Scholar 

  74. Ivarsson, K., Ekerydh, A., Fyhr, I. M., Janson, P. O., and Brannstrom, M. (2000) Acta Obstet. Gynecol. Scand., 79, 777–784.

    Article  PubMed  Google Scholar 

  75. Lin, Y., Huang, R., Chen, L., Li, S., Shi, Q., Jordan, C., and Huang R. P. (2004) Int. J. Cancer, 109, 507–515.

    Article  PubMed  Google Scholar 

  76. Garrido, C., Gurbuxani, S., Ravagnan, L., and Kroemer, G. (2001) Biochem. Biophys. Res. Commun., 286, 433–442.

    Article  PubMed  Google Scholar 

  77. Mosser, D. D., and Morimoto, R. I. (2004) Oncogene, 23, 2907–2918.

    Article  PubMed  Google Scholar 

  78. Beere, H. M., Wolf, B. B., Cain, K., Mosser, D. D., Mahboubi, A., Kuwana, T., Tailor, P., Morimoto, R. I., Cohen, G. M., and Green, D. R. (2000) Nat. Cell. Biol., 2, 469–475.

    Article  PubMed  Google Scholar 

  79. Luft, J. C., and Dix, D. J. (1999) Cell Stress Chaperones, 4, 162–170.

    Article  PubMed  Google Scholar 

  80. Eddy, E. M. (1999) Rev. Reprod., 4, 23–30.

    Article  PubMed  Google Scholar 

  81. Hayward, B. E., and Bonthron, D. T. (1998) Eur. J. Biochem., 257, 85–91.

    Article  PubMed  Google Scholar 

  82. Rangaswamy, V., and Altekar, W. (1994) J. Bacteriol., 176, 5505–5512.

    PubMed  Google Scholar 

  83. Heinz, F., Lamprecht, W., and Kirsch, J. (1968) J. Clin. Invest., 47, 1826–1832.

    PubMed  Google Scholar 

  84. Nielsen, F. C., and Gammeltoft, S. (1990) FEBS Lett., 262, 142–144.

    Article  PubMed  Google Scholar 

  85. Wary, K. W., Thakker, G. D., Humtsoe, J. O., and Yang, J. (2003) Mol. Cancer, 2, 25–36.

    Article  PubMed  Google Scholar 

  86. Kartasheva, N. N., Lenz-Bauer, C., Hartmann, O., Schafer, H., Eilers, M., and Dobbelstein, M. (2003) Oncogene, 22, 8246–8254.

    Article  PubMed  Google Scholar 

  87. Stiewe, T., Stanelle, J., Theseling, C. C., Pollmeier, B., Beitzinger, M., and Putzer, M. (2003) J. Biol. Chem., 278, 14230–14236.

    Article  PubMed  Google Scholar 

  88. Besset, V., Rhee, K., and Wolgemuth D. J. (1999) Cell Growth Differ., 10, 173–181.

    PubMed  Google Scholar 

  89. Herskovits, A. Z., and Davies, P. (2004) Gene, 328, 59–67.

    Article  PubMed  Google Scholar 

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Translated from Biokhimiya, Vol. 70, No. 9, 2005, pp. 1157–1176.

Original Russian Text Copyright © 2005 by Morgunkova.

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Morgunkova, A.A. The p53 Gene Family: Control of Cell Proliferation and Developmental Programs. Biochemistry (Moscow) 70, 955–971 (2005). https://doi.org/10.1007/s10541-005-0210-4

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