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Coordinated interaction of multifunctional members of the p53 family determines many key processes in multicellular organisms

  • Molecular Aspects of the Regulation of Apoptosis
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Abstract

For the first time, p53 was found in complex with the viral large T-antigen in cells transformed with the small DNA virus SV40. p53 cDNA was cloned in the early 1980s, and the full-length p53 gene was cloned soon afterwards. The p53 family is comprised of three genes—TP53, TP63, and TP73—each of which is expressed as a set of structurally and functionally different isoforms. All of them intensely interact with each other, forming a united functional network of proteins. The review discusses the evolution of the p53 family and the significance of all its members in embryo development, reproduction, regeneration, regulation of aging and lifespan, and defense against cancer. Special attention is paid to the role of poorly studied members of the p53 family, p63 and p73, in carcinogenesis and tumor progression. Different isoforms of these proteins might exert opposite effects on these processes.

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Abbreviations

Cep1:

C. elegans protein homologous to p53/p73

p53-RE-p53:

response element

DBD-DNA:

binding domain

OD:

oligomerization domain

SAM:

sterile α motif

TAD:

transactivation domain

TA:

transcriptionally active isoform

δTA:

or δN-isoform with a deletion of the N-terminal TAD

TID:

transcription inhibition domain

MEF:

mouse embryonic fibroblast

References

  1. Chumakov P.M., Iotseva V.S., Georgiev G.P. 1982. Isolation of a plasmid clone containing mRNA sequences for nonviral murine T antigen. Dokl. Akad. Nauk SSSR. 267, 1272–1275.

    PubMed  CAS  Google Scholar 

  2. Oren M., Levine A.J. 1983. Molecular cloning of a cDNA specific for the murine p53 cellular tumor antigen. Proc. Natl. Acad. Sci. U.S.A. 80, 56–59.

    PubMed  CAS  Google Scholar 

  3. Lane D.P. 1992. Cancer: p53, guardian of the genome. Nature. 358, 15–16.

    PubMed  CAS  Google Scholar 

  4. Riley T., Sontag E., Chen P., Levine A. 2008. Transcriptional control of human p53-regulated genes. Nature Rev. Mol. Cell Biol. 9, 402–412.

    CAS  Google Scholar 

  5. Chumakov P.M. 2007. Protein p53 and its universal functions in a multicellular organism. Usp. Biol. Khim. 47, 3–52.

    CAS  Google Scholar 

  6. Almazov V.P., Kochetkov D.V., Chumakov P.M. 2007. Use of p53 for therapy of human cancer. Mol. Biol. (Moscow). 41, 863–878.

    CAS  Google Scholar 

  7. Melino G., Lu X., Gasco M., Crook T., Knight R.A. 2003. Functional regulation of p73 and p63: Development and cancer. Trends Biochem. Sci. 28, 663–670.

    PubMed  CAS  Google Scholar 

  8. Belyi V.A., Levine A.J. 2009. One billion years of p53/p63/p73 evolution. Proc. Natl. Acad. Sci. U.S.A. 106, 17609–17610.

    PubMed  CAS  Google Scholar 

  9. Brandt T., Petrovich M., Joerger A.C., Veprintsev D.B. 2009. Conservation of DNA-binding specificity and oligomerisation properties within the p53 family. BMC Genomics. 10, 628.

    PubMed  Google Scholar 

  10. el-Deiry W.S., Kern S.E., Pietenpol J.A., Kinzler K.W., Vogelstein B. 1992. Definition of a consensus binding site for p53. Nature Genet. 1, 45–49.

    PubMed  CAS  Google Scholar 

  11. Funk W.D., Pak D.T., Karas R.H., Wright W.E., Shay J.W. 1992. A transcriptionally active DNA-binding site for human p53 protein complexes. Mol. Cell Biol. 12, 2866–2871.

    PubMed  CAS  Google Scholar 

  12. Perez C.A., Ott J., Mays D.J., Pietenpol J.A. 2007. p63 consensus DNA-binding site: Identification, analysis and application into a p63MH algorithm. Oncogene. 26, 7363–7370.

    PubMed  CAS  Google Scholar 

  13. Lokshin M., Li Y., Gaiddon C., Prives C. 2007. p53 and p73 display common and distinct requirements for sequence specific binding to DNA. Nucleic Acids Res. 35, 340–352.

    PubMed  CAS  Google Scholar 

  14. Davison T.S., Vagner C., Kaghad M., Ayed A., Caput D., Arrowsmith C.H. 1999. p73 and p63 are homotetramers capable of weak heterotypic interactions with each other but not with p53. J. Biol. Chem. 274, 18709–18714.

    PubMed  CAS  Google Scholar 

  15. Serber Z., Lai H.C., Yang A., Ou H.D., Sigal M.S., Kelly A.E., Darimont B.D., Duijf P.H., van Bokhoven H., McKeon F., Dotsch V. 2002. A C-terminal inhibitory domain controls the activity of p63 by an intramolecular mechanism. Mol. Cell Biol. 22, 8601–8611.

    PubMed  CAS  Google Scholar 

  16. Liu G., Chen X. 2005. The C-terminal sterile alpha motif and the extreme C-terminus regulate the transcriptional activity of the alpha isoform of p73. J. Biol. Chem. 278, 46878–46885.

    Google Scholar 

  17. Barrera F.N., Poveda J.A., Gonzalez-Ros J.M., Neira J.L. 2003. Binding of the C-terminal sterile alpha motif (SAM) domain of human p73 to lipid membranes. J. Biol. Chem. 278, 46878–46885.

    PubMed  CAS  Google Scholar 

  18. Scaruffi P., Casciano I., Masiero L., Basso G., Romani M., Tonini G. P. 2000. Lack of p73 expression in mature B-ALL and identification of three new splicing variants restricted to pre B and C-ALL indicate a role of p73 in B cell ALL differentiation. Leukemia. 14, 518–519.

    PubMed  CAS  Google Scholar 

  19. De Laurenzi V., Costanzo A., Barcaroli D., Terrinoni A., Falco M., Annicchiarico-Petruzzelli M., Levrero M., Melino G. 1998. Two new p73 splice variants, gamma and delta, with different transcriptional activity. J. Exp. Med. 188, 1763–1768.

    PubMed  Google Scholar 

  20. 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., Caput D. 1997. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers. Cell. 90, 809–819.

    PubMed  CAS  Google Scholar 

  21. Yang A., Kaghad M., Wang Y., Gillett E., Fleming M.D., Dotsch V., Andrews N.C., Caput D., McKeon F. 1998. p63, a p53 homolog at 3q27–29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol. Cell. 2, 305–316.

    PubMed  CAS  Google Scholar 

  22. Zaika A.I., Kovalev S., Marchenko N.D., Moll U.M. 1999. Overexpression of the wild type p73 gene in breast cancer tissues and cell lines. Cancer Res. 59, 3257–3263.

    PubMed  CAS  Google Scholar 

  23. Ueda Y., Hijikata M., Takagi S., Chiba T., Shimotohno K. 1999. New p73 variants with altered C-terminal structures have varied transcriptional activities. Oncogene. 18, 4993–4998.

    PubMed  CAS  Google Scholar 

  24. Ishimoto O., Kawahara C., Enjo K., Obinata M., Nukiwa T., Ikawa S. 2002. Possible oncogenic potential of DeltaNp73: a newly identified isoform of human p73. Cancer Res. 62, 636–641.

    PubMed  CAS  Google Scholar 

  25. Stiewe T., Zimmermann S., Frilling A., Esche H., Putzer B.M. 2002. Transactivation-deficient DeltaTA-p73 acts as an oncogene. Cancer Res. 62, 3598–3602.

    PubMed  CAS  Google Scholar 

  26. Yang A., Walker N., Bronson R., Kaghad M., Oosterwegel M., Bonnin J., Vagner C., Bonnet H., Dikkes P., Sharpe A., McKeon F., Caput D. 2000. p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours. Nature. 404, 99–103.

    PubMed  CAS  Google Scholar 

  27. Sayan A.E., Roperch J.P., Sayan B.S., Rossi M., Pinkoski M.J., Knight R.A., Willis A.E., Melino G. 2007. Generation of DeltaTAp73 proteins by translation from a putative internal ribosome entry site. Ann. N.Y. Acad. Sci. 1095, 315–324.

    PubMed  CAS  Google Scholar 

  28. Khoury M.P., Bourdon J.C. 2010. The isoforms of the p53 protein. Cold Spring Harbor Perspect. Biol. 2, a000927.

    Google Scholar 

  29. Sayan A.E., Sayan B.S., Gogvadze V., Dinsdale D., Nyman U., Hansen T.M., Zhivotovsky B., Cohen G.M., Knight R.A., Melino G. 2008. P73 and caspasecleaved p73 fragments localize to mitochondria and augment TRAIL-induced apoptosis. Oncogene. 27, 4363–4372.

    PubMed  CAS  Google Scholar 

  30. Speidel D. 2010. Transcription-independent p53 apoptosis: An alternative route to death. Trends Cell Biol. 20, 14–24.

    PubMed  CAS  Google Scholar 

  31. Fernandes A.D., Atchley W.R. 2008. Biochemical and functional evidence of p53 homology is inconsistent with molecular phylogenetics for distant sequences. J. Mol. Evol. 67, 51–67.

    PubMed  CAS  Google Scholar 

  32. Joerger A.C., Fersht A.R. 2007. Structure-functionrescue: The diverse nature of common p53 cancer mutants. Oncogene. 26, 2226–2242.

    PubMed  CAS  Google Scholar 

  33. Petitjean A., Mathe E., Kato S., Ishioka C., Tavtigian S.V., Hainaut P., Olivier M. 2007. Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: Lessons from recent developments in the IARC TP53 database. Hum. Mutat. 28, 622–629.

    PubMed  CAS  Google Scholar 

  34. Menendez D., Inga A., Resnick M.A. 2009. The expanding universe of p53 targets. Nature Rev. Cancer. 9, 724–737.

    CAS  Google Scholar 

  35. Harms K., Nozell S., Chen X. 2004. The common and distinct target genes of the p53 family transcription factors. Cell Mol. Life Sci. 61, 822–842.

    PubMed  CAS  Google Scholar 

  36. Perez C.A., Pietenpol J.A. 2007. Transcriptional programs regulated by p63 in normal epithelium and tumors. Cell Cycle. 6, 246–254.

    PubMed  CAS  Google Scholar 

  37. Fontemaggi G., Kela I., Amariglio N., Rechavi G., Krishnamurthy J., Strano S., Sacchi A., Givol D., Blandino G. 2002. Identification of direct p73 target genes combining DNA microarray and chromatin immunoprecipitation analyses. J. Biol. Chem. 277, 43359–43368.

    PubMed  CAS  Google Scholar 

  38. Lin Y.L., Sengupta S., Gurdziel K., Bell G.W., Jacks T., Flores E.R. 2009. p63 and p73 transcriptionally regulate genes involved in DNA repair. PLoS Genet. 5, e1000680.

    PubMed  Google Scholar 

  39. Vilgelm A., Wei J.X., Piazuelo M.B., Washington M.K., Prassolov V., El-Rifai W., Zaika A. 2008. DeltaNp73alpha regulates MDR1 expression by inhibiting p53 function. Oncogene. 27, 2170–2176.

    PubMed  CAS  Google Scholar 

  40. Stiewe T., Theseling C.C., Putzer B.M. 2002. Transactivation-deficient Delta TA-p73 inhibits p53 by direct competition for DNA binding: Implications for tumorigenesis. J. Biol. Chem. 277, 14177–14185.

    PubMed  CAS  Google Scholar 

  41. Nakagawa T., Takahashi M., Ozaki T., Watanabe Ki K., Todo S., Mizuguchi H., Hayakawa T., Nakagawara A. 2002. Autoinhibitory regulation of p73 by Delta Np73 to modulate cell survival and death through a p73-specific target element within the Delta Np73 promoter. Mol. Cell Biol. 22, 2575–2585.

    PubMed  CAS  Google Scholar 

  42. Zaika A.I., Slade N., Erster S.H., Sansome C., Joseph T.W., Pearl M., Chalas E., Moll U.M. 2002. DeltaNp73, a dominant-negative inhibitor of wild-type p53 and TAp73, is up-regulated in human tumors. J. Exp. Med. 196, 765–780.

    PubMed  CAS  Google Scholar 

  43. 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, 3193–3205.

    PubMed  CAS  Google Scholar 

  44. Kartasheva N.N., Lenz-Bauer C., Hartmann O., Schafer H., Eilers M., Dobbelstein M. 2003. DeltaNp73 can modulate the expression of various genes in a p53-independent fashion. Oncogene. 22, 8246–8254.

    PubMed  CAS  Google Scholar 

  45. Liu G., Nozell S., Xiao H., Chen X. 2004. DeltaNp73beta is active in transactivation and growth suppression. Mol. Cell Biol. 24, 487–501.

    PubMed  CAS  Google Scholar 

  46. Tanaka Y., Kameoka M., Itaya A., Ota K., Yoshihara K. 2004. Regulation of HSF1-responsive gene expression by N-terminal truncated form of p73alpha. Biochem. Biophys. Res. Commun. 317, 865–872.

    PubMed  CAS  Google Scholar 

  47. Wu G., Nomoto S., Hoque M.O., Dracheva T., Osada M., Lee C.C., Dong S.M., Guo Z., Benoit N., Cohen Y., Rechthand P., Califano J., Moon C.S., Ratovitski E., Jen J., Sidransky D., Trink B. 2003. DeltaNp63alpha and TAp63alpha regulate transcription of genes with distinct biological functions in cancer and development. Cancer Res. 63, 2351–2357.

    PubMed  CAS  Google Scholar 

  48. Wu G., Osada M., Guo Z., Fomenkov A., Begum S., Zhao M., Upadhyay S., Xing M., Wu F., Moon C., Westra W.H., Koch W.M., Mantovani R., Califano J.A., Ratovitski E., Sidransky D., Trink B. 2005. DeltaNp63alpha up-regulates the Hsp70 gene in human cancer. Cancer Res. 65, 758–766.

    PubMed  CAS  Google Scholar 

  49. Ghosh A., Stewart D., Matlashewski G. 2004. Regulation of human p53 activity and cell localization by alternative splicing. Mol. Cell Biol. 24, 7987–7997.

    PubMed  CAS  Google Scholar 

  50. Courtois S., Verhaegh G., North S., Luciani M.G., Lassus P., Hibner U., Oren M., Hainaut P. 2002. DeltaN-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53. Oncogene. 21, 6722–6728.

    PubMed  CAS  Google Scholar 

  51. Nedelcu A.M., Tan C. 2007. Early diversification and complex evolutionary history of the p53 tumor suppressor gene family. Dev. Genes Evol. 217, 801–806.

    PubMed  Google Scholar 

  52. Lane D.P., Cheok C.F., Brown C., Madhumalar A., Ghadessy F.J., Verma C. 2010. Mdm2 and p53 are highly conserved from placozoans to man. Cell Cycle. 9, 540–547.

    PubMed  CAS  Google Scholar 

  53. Srivastava M., Begovic E., Chapman J., Putnam N.H., Hellsten U., Kawashima T., Kuo A., Mitros T., Salamov A., Carpenter M.L., Signorovitch A.Y., Moreno M.A., Kamm K., Grimwood J., Schmutz J., Shapiro H., Grigoriev I.V., Buss L.W., Schierwater B., Dellaporta S.L., Rokhsar D. S. 2008. The Trichoplax genome and the nature of placozoans. Nature. 454, 955–960.

    PubMed  CAS  Google Scholar 

  54. Lane D.P., Cheok C.F., Brown C.J., Madhumalar A., Ghadessy F.J., Verma C. 2010. The Mdm2 and p53 genes are conserved in the Arachnids. Cell Cycle. 9, 748–754.

    PubMed  CAS  Google Scholar 

  55. Kelley M.L., Winge P., Heaney J.D., Stephens R.E., Farell J.H., van Beneden R.J., Reinisch C.L., Lesser M.P., Walker C.W. 2001. Expression of homologues for p53 and p73 in the softshell clam (Mya arenaria), a naturally occurring model for human cancer. Oncogene. 20, 748–758.

    PubMed  CAS  Google Scholar 

  56. Derry W.B., Putzke A.P., Rothman J.H. 2001. Caenorhabditis elegans p53: Role in apoptosis, meiosis, and stress resistance. Science. 294, 591–595.

    PubMed  CAS  Google Scholar 

  57. Schumacher B., Hofmann K., Boulton S., Gartner A. 2001. The C. elegans homolog of the p53 tumor suppressor is required for DNA damage-induced apoptosis. Curr. Biol. 11, 1722–1727.

    PubMed  CAS  Google Scholar 

  58. Jin S., Martinek S., Joo W.S., Wortman J.R., Mirkovic N., Sali A., Yandell M.D., Pavletich N.P., Young M.W., Levine A.J. 2000. Identification and characterization of a p53 homologue in Drosophila melanogaster. Proc. Natl. Acad. Sci. U.S.A. 97, 7301–7306.

    PubMed  CAS  Google Scholar 

  59. Ollmann M., Young L.M., Di Como C.J., Karim F., Belvin M., Robertson S., Whittaker K., Demsky M., Fisher W.W., Buchman A., Duyk G., Friedman L., Prives C., Kopczynski C. 2000. Drosophila p53 is a structural and functional homolog of the tumor suppressor p53. Cell. 101, 91–101.

    PubMed  CAS  Google Scholar 

  60. Pankow S., Bamberger C. 2007. The p53 tumor suppressor-like protein nvp63 mediates selective germ cell death in the sea anemone Nematostella vectensis. PLoS One. 2, e782.

    PubMed  Google Scholar 

  61. Ou H.D., Lohr F., Vogel V., Mantele W., Dotsch V. 2007. Structural evolution of C-terminal domains in the p53 family. EMBO J. 26, 3463–3473.

    PubMed  CAS  Google Scholar 

  62. Rutkowski R., Hofmann K., Gartner A. 2010. Phylogeny and function of the invertebrate p53 superfamily. Cold Spring Harbor Perspect. Biol. 2, a001131.

    Google Scholar 

  63. Belyi V.A., Ak P., Markert E., Wang H., Hu W., Puzio-Kuter A., Levine A.J. 2010. The origins and evolution of the p53 family of genes. Cold Spring Harbor Perspect. Biol. 2, a001198.

    Google Scholar 

  64. Brodsky M.H., Nordstrom W., Tsang G., Kwan E., Rubin G.M., Abrams J.M. 2000. Drosophila p53 binds a damage response element at the reaper locus. Cell. 101, 103–113.

    PubMed  CAS  Google Scholar 

  65. Sogame N., Kim M., Abrams J.M. 2003. Drosophila p53 preserves genomic stability by regulating cell death. Proc. Natl. Acad. Sci. U.S.A. 100, 4696–4701.

    PubMed  CAS  Google Scholar 

  66. Lee J.H., Lee E., Park J., Kim E., Kim J., Chung J. 2003. In vivo p53 function is indispensable for DNA damage-induced apoptotic signaling in Drosophila. FEBS Lett. 550, 5–10.

    PubMed  CAS  Google Scholar 

  67. Arum O., Johnson T.E. 2007. Reduced expression of the Caenorhabditis elegans p53 ortholog cep-1 results in increased longevity. J. Gerontol. A, Biol. Sci. Med. Sci. 62, 951–959.

    Google Scholar 

  68. Tavernarakis N., Pasparaki A., Tasdemir E., Maiuri M.C., Kroemer G. 2008. The effects of p53 on whole organism longevity are mediated by autophagy. Autophagy. 4, 870–873.

    PubMed  CAS  Google Scholar 

  69. Bauer J.H., Poon P.C., Glatt-Deeley H., Abrams J.M., Helfand S.L. 2005. Neuronal expression of p53 dominant-negative proteins in adult Drosophila melanogaster extends life span. Curr. Biol. 15, 2063–2068.

    PubMed  CAS  Google Scholar 

  70. Bauer J.H., Chang C., Morris S.N., Hozier S., Andersen S., Waitzman J.S., Helfand S.L. 2007. Expression of dominant-negative Dmp53 in the adult fly brain inhibits insulin signaling. Proc. Natl. Acad. Sci. U.S.A. 104, 13355–13360.

    PubMed  CAS  Google Scholar 

  71. Suh E.K., Yang A., Kettenbach A., Bamberger C., Michaelis A.H., Zhu Z., Elvin J.A., Bronson R.T., Crum C.P., McKeon F. 2006. p63 protects the female germ line during meiotic arrest. Nature. 444, 624–628.

    PubMed  CAS  Google Scholar 

  72. Tomasini R., Tsuchihara K., Wilhelm M., Fujitani M., Rufini A., Cheung C.C., Khan F., Itie-Youten A., Wakeham A., Tsao M.S., Iovanna J.L., Squire J., Jurisica I., Kaplan D., Melino G., Jurisicova A., Mak T.W. 2008. TAp73 knockout shows genomic instability with infertility and tumor suppressor functions. Genes Dev. 22, 2677–2691.

    PubMed  CAS  Google Scholar 

  73. Hasegawa M., Zhang Y., Niibe H., Terry N.H., Meistrich M.L. 1998. Resistance of differentiating spermatogonia to radiation-induced apoptosis and loss in p53-deficient mice. Radiat. Res. 149, 263–270.

    PubMed  CAS  Google Scholar 

  74. Hu W. 2009. The role of p53 gene family in reproduction. Cold Spring Harbor Perspect. Biol. 1, a001073.

    Google Scholar 

  75. Hu W., Feng Z., Teresky A.K., Levine A.J. 2007. p53 regulates maternal reproduction through LIF. Nature. 450, 721–724.

    PubMed  CAS  Google Scholar 

  76. Crum C.P., McKeon F.D. 2010. p63 in epithelial survival, germ cell surveillance, and neoplasia. Annu. Rev. Pathol. 5, 349–371.

    PubMed  CAS  Google Scholar 

  77. Laurikkala J., Mikkola M.L., James M., Tummers M., Mills A.A., Thesleff I. 2006. p63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation. Development. 133, 1553–1563.

    PubMed  CAS  Google Scholar 

  78. Rinne T., Brunner H.G., van Bokhoven H. 2007. p63-associated disorders. Cell Cycle. 6, 262–268.

    PubMed  CAS  Google Scholar 

  79. Yang A., Schweitzer R., Sun D., Kaghad M., Walker N., Bronson R.T., Tabin C., Sharpe A., Caput D., Crum C., McKeon F. 1999. p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development. Nature. 398, 714–718.

    PubMed  CAS  Google Scholar 

  80. Mills A.A., Zheng B., Wang X.J., Vogel H., Roop D.R., Bradley A. 1999. p63 is a p53 homologue required for limb and epidermal morphogenesis. Nature. 398, 708–713.

    PubMed  CAS  Google Scholar 

  81. Senoo M., Pinto F., Crum C.P., McKeon F. 2007. p63 is essential for the proliferative potential of stem cells in stratified epithelia. Cell. 129, 523–536.

    PubMed  CAS  Google Scholar 

  82. Koster M.I., Kim S., Mills A.A., DeMayo F.J., Roop D.R. 2004. p63 is the molecular switch for initiation of an epithelial stratification program. Genes Dev. 18, 126–131.

    PubMed  CAS  Google Scholar 

  83. Koster M.I., Dai D., Marinari B., Sano Y., Costanzo A., Karin M., Roop D.R. 2007. p63 induces key target genes required for epidermal morphogenesis. Proc. Natl. Acad. Sci. U.S.A. 104, 3255–3260.

    PubMed  CAS  Google Scholar 

  84. Candi E., Rufini A., Terrinoni A., Dinsdale D., Ranalli M., Paradisi A., De Laurenzi V., Spagnoli L.G., Catani M.V., Ramadan S., Knight R.A., Melino G. 2006. Differential roles of p63 isoforms in epidermal development: selective genetic complementation in p63 null mice. Cell Death Differ. 13, 1037–1047.

    PubMed  CAS  Google Scholar 

  85. Truong A.B., Kretz M., Ridky T.W., Kimmel R., Khavari P.A. 2006. p63 regulates proliferation and differentiation of developmentally mature keratinocytes. Genes Dev. 20, 3185–3197.

    PubMed  CAS  Google Scholar 

  86. Wilhelm M.T., Rufini A., Wetzel M.K., Tsuchihara K., Inoue S., Tomasini R., Itie-Youten A., Wakeham A., Arsenian-Henriksson M., Melino G., Kaplan D.R., Miller F.D., Mak T.W. 2010. Isoform-specific p73 knockout mice reveal a novel role for ΔNp73 in the DNA damage response pathway. Genes Dev. 24, 549–560.

    PubMed  CAS  Google Scholar 

  87. Hoever M., Clement J.H., Wedlich D., Montenarh M., Knochel W. 1994. Overexpression of wild-type p53 interferes with normal development in Xenopus laevis embryos. Oncogene. 9, 109–120.

    PubMed  CAS  Google Scholar 

  88. Nicol C.J., Harrison M.L., Laposa R.R., Gimelshtein I.L., Wells P.G. 1995. A teratologic suppressor role for p53 in benzo[a]pyrene-treated transgenic p53-deficient mice. Nature Genet. 10, 181–187.

    PubMed  CAS  Google Scholar 

  89. Norimura T., Nomoto S., Katsuki M., Gondo Y., Kondo S. 1996. p53-dependent apoptosis suppresses radiation-induced teratogenesis. Nature Med. 2, 577–580.

    PubMed  CAS  Google Scholar 

  90. Jones S.N., Roe A.E., Donehower L.A., Bradley A. 1995. Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53. Nature. 378, 206–208.

    PubMed  CAS  Google Scholar 

  91. Erster S., Palacios G., Rosenquist T., Chang C., Moll U.M. 2006. Deregulated expression of ΔNp73α causes early embryonic lethality. Cell Death Differ. 13, 170–173

    PubMed  CAS  Google Scholar 

  92. Huttinger-Kirchhof N., Cam H., Griesmann H., Hofmann L., Beitzinger M., Stiewe T. 2006. The p53 family inhibitor ΔNp73 interferes with multiple developmental programs. Cell Death Differ. 13, 174–177.

    PubMed  CAS  Google Scholar 

  93. Dugani C.B., Paquin A., Fujitani M., Kaplan D.R., Miller F.D. 2009. p63 antagonizes p53 to promote the survival of embryonic neural precursor cells. J. Neurosci. 29, 6710–6721.

    PubMed  CAS  Google Scholar 

  94. Lee A.F., Ho D.K., Zanassi P., Walsh G.S., Kaplan D.R., Miller F.D. 2004. Evidence that ΔNp73 promotes neuronal survival by p53-dependent and p53-independent mechanisms. J. Neurosci. 24, 9174–9184.

    PubMed  CAS  Google Scholar 

  95. Pozniak C.D., Radinovic S., Yang A., McKeon F., Kaplan D.R., Miller F.D. 2000. An anti-apoptotic role for the p53 family member, p73, during developmental neuron death. Science. 289, 304–306.

    PubMed  CAS  Google Scholar 

  96. Dumble M., Moore L., Chambers S.M., Geiger H., van Zant G., Goodell M.A., Donehower L.A. 2007. The impact of altered p53 dosage on hematopoietic stem cell dynamics during aging. Blood. 109, 1736–1742.

    PubMed  CAS  Google Scholar 

  97. Tissir F., Ravni A., Achouri Y., Riethmacher D., Meyer G., Goffinet A.M. 2009. ΔNp73 regulates neuronal survival in vivo. Proc. Natl. Acad. Sci. U.S.A. 106, 16871–16876.

    PubMed  CAS  Google Scholar 

  98. Pozniak C.D., Barnabe-Heider F., Rymar V.V., Lee A.F., Sadikot A.F., Miller F.D. 2002. p73 is required for survival and maintenance of CNS neurons. J. Neurosci. 22, 9800–9809.

    PubMed  CAS  Google Scholar 

  99. Sahin E., Depinho R.A. 2010. Linking functional decline of telomeres, mitochondria and stem cells during ageing. Nature. 464, 520–528.

    PubMed  CAS  Google Scholar 

  100. Keyes W.M., Wu Y., Vogel H., Guo X., Lowe S.W., Mills A.A. 2005. p63 deficiency activates a program of cellular senescence and leads to accelerated aging. Genes Dev. 19, 1986–1999.

    PubMed  CAS  Google Scholar 

  101. Su X., Paris M., Gi Y.J., Tsai K.Y., Cho M.S., Lin Y.L., Biernaskie J.A., Sinha S., Prives C., Pevny L.H., Miller F.D., Flores E.R. 2009. TAp63 prevents premature aging by promoting adult stem cell maintenance. Cell Stem Cell. 5, 64–75.

    PubMed  CAS  Google Scholar 

  102. Chin L., Artandi S.E., Shen Q., Tam A., Lee S.L., Gottlieb G.J., Greider C.W., DePinho R.A. 1999. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell. 97, 527–538.

    PubMed  CAS  Google Scholar 

  103. Sablina A.A., Budanov A.V., Ilyinskaya G.V., Agapova L.S., Kravchenko J.E., Chumakov P.M. 2005. The antioxidant function of the p53 tumor suppressor. Nature Med. 11, 1306–1313.

    PubMed  CAS  Google Scholar 

  104. Feng Z., Zhang H., Levine A.J., Jin S. 2005. The coordinate regulation of the p53 and mTOR pathways in cells. Proc. Natl. Acad. Sci. U.S.A. 102, 8204–8209.

    PubMed  CAS  Google Scholar 

  105. Matheu A., Maraver A., Klatt P., Flores I., Garcia-Cao I., Borras C., Flores J.M., Vina J., Blasco M.A., Serrano M. 2007. Delayed ageing through damage protection by the Arf/p53 pathway. Nature. 448, 375–379.

    PubMed  CAS  Google Scholar 

  106. Vousden K.H., Prives C. 2009. Blinded by the light: The growing complexity of p53. Cell. 137, 413–431.

    PubMed  CAS  Google Scholar 

  107. Hong L.Z., Zhao X.Y., Zhang H.L. 2010. p53-mediated neuronal cell death in ischemic brain injury. Neurosci. Bull. 26, 232–240.

    PubMed  CAS  Google Scholar 

  108. Naito A.T., Okada S., Minamino T., Iwanaga K., Liu M.L., Sumida T., Nomura S., Sahara N., Mizoroki T., Takashima A., Akazawa H., Nagai T., Shiojima I., Komuro I. 2010. Promotion of CHIP-mediated p53 degradation protects the heart from ischemic injury. Circ. Res. 106, 1692–1702.

    PubMed  CAS  Google Scholar 

  109. Culmsee C., Mattson M. P. 2005. p53 in neuronal apoptosis. Biochem. Biophys. Res. Commun. 331, 761–777.

    PubMed  CAS  Google Scholar 

  110. Donehower L.A., Harvey M., Slagle B.L., McArthur M.J., Montgomery C.A., Jr., Butel J.S., Bradley A. 1992. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature. 356, 215–221.

    PubMed  CAS  Google Scholar 

  111. Vogelstein B. 1990. Cancer: A deadly inheritance. Nature. 348, 681–682.

    PubMed  CAS  Google Scholar 

  112. Vilgelm A., El-Rifai W., Zaika A. 2008. Therapeutic prospects for p73 and p63: Rising from the shadow of p53. Drug Resist. Update. 11, 152–163.

    CAS  Google Scholar 

  113. Collavin L., Lunardi A., Del Sal G. 2010. p53-family proteins and their regulators: Hubs and spokes in tumor suppression. Cell Death Differ. 17, 901–911.

    PubMed  CAS  Google Scholar 

  114. Melino G., De Laurenzi V., Vousden K.H. 2002. p73: Friend or foe in tumorigenesis. Nature Rev. Cancer. 2, 605–615.

    CAS  Google Scholar 

  115. Moll U.M., Slade N. 2004. p63 and p73: Roles in development and tumor formation. Mol. Cancer Res. 2, 371–386.

    PubMed  CAS  Google Scholar 

  116. Pluta A., Nyman U., Joseph B., Robak T., Zhivotovsky B., Smolewski P. 2006. The role of p73 in hematological malignancies. Leukemia. 20, 757–766.

    PubMed  CAS  Google Scholar 

  117. Garcia-Manero G., Daniel J., Smith T.L., Kornblau S.M., Lee M.S., Kantarjian H.M., Issa J.P. 2002. DNA methylation of multiple promoter-associated CpG islands in adult acute lymphocytic leukemia. Clin. Cancer Res. 8, 2217–2224.

    PubMed  CAS  Google Scholar 

  118. Deyoung M.P., Ellisen L.W. 2007. p63 and p73 in human cancer: Defining the network. Oncogene. 26, 5169–5183.

    PubMed  CAS  Google Scholar 

  119. Koga F., Kawakami S., Fujii Y., Saito K., Ohtsuka Y., Iwai A., Ando N., Takizawa T., Kageyama Y., Kihara K. 2003. Impaired p63 expression associates with poor prognosis and uroplakin III expression in invasive urothelial carcinoma of the bladder. Clin. Cancer Res. 9, 5501–5507.

    PubMed  CAS  Google Scholar 

  120. Stefansson I.M., Salvesen H.B., Akslen L.A. 2006. Loss of p63 and cytokeratin 5/6 expression is associated with more aggressive tumors in endometrial carcinoma patients. Int. J. Cancer. 118, 1227–1233.

    PubMed  CAS  Google Scholar 

  121. Urist M.J., Di Como C.J., Lu M.L., Charytonowicz E., Verbel D., Crum C.P., Ince T.A., McKeon F.D., Cordon-Cardo C. 2002. Loss of p63 expression is associated with tumor progression in bladder cancer. Am. J. Pathol. 161, 1199–1206.

    PubMed  CAS  Google Scholar 

  122. Lee C.H., Espinosa I., Jensen K.C., Subramanian S., Zhu S.X., Varma S., Montgomery K.D., Nielsen T.O., van de Rijn M., West R.B. 2008. Gene expression profiling identifies p63 as a diagnostic marker for giant cell tumor of the bone. Mol. Pathol. 21, 531–539.

    CAS  Google Scholar 

  123. Frebourg T., Malkin D., Friend S. 1991. Cancer risks from germ line tumor suppressor gene mutations. Princess Takamatsu Symp. 22, 61–70.

    PubMed  CAS  Google Scholar 

  124. Celli J., Duijf P., Hamel B.C., Bamshad M., Kramer B., Smits A.P., Newbury-Ecob R., Hennekam R.C., van Buggenhout G., van Haeringen A., Woods C.G., van Essen A.J., de Waal R., Vriend G., Haber D.A., Yang A., McKeon F., Brunner H.G., van Bokhoven H. 1999. Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome. Cell. 99, 143–153.

    PubMed  CAS  Google Scholar 

  125. Schwartz D.I., Lindor N.M., Walsh-Vockley C., Roche P.C., Mai M., Smith D.I., Liu W., Couch F.J. 1999. p73 mutations are not detected in sporadic and hereditary breast cancer. Breast Cancer Res. Treat. 58, 25–29.

    PubMed  CAS  Google Scholar 

  126. Peters M.A., Janer M., Kolb S., Jarvik G.P., Ostrander E.A., Stanford J.L. 2001. Germline mutations in the p73 gene do not predispose to familial prostate-brain cancer. Prostate. 48, 292–296.

    PubMed  CAS  Google Scholar 

  127. Flores E.R., Sengupta S., Miller J.B., Newman J.J., Bronson R., Crowley D., Yang A., McKeon F., Jacks T. 2005. Tumor predisposition in mice mutant for p63 and p73: Evidence for broader tumor suppressor functions for the p53 family. Cancer Cell. 7, 363–373.

    PubMed  CAS  Google Scholar 

  128. Nemajerova A., Palacios G., Nowak N.J., Matsui S., Petrenko O. 2009. Targeted deletion of p73 in mice reveals its role in T cell development and lymphomagenesis. PLoS One. 4, e7784.

    PubMed  Google Scholar 

  129. Keyes W.M., Vogel H., Koster M.I., Guo X., Qi Y., Petherbridge K.M., Roop D.R., Bradley A., Mills A.A. 2006. p63 heterozygous mutant mice are not prone to spontaneous or chemically induced tumors. Proc. Natl. Acad. Sci. U.S.A. 103, 8435–8440.

    PubMed  CAS  Google Scholar 

  130. Guo X., Keyes W.M., Papazoglu C., Zuber J., Li W., Lowe S.W., Vogel H., Mills A.A. 2009. TAp63 induces senescence and suppresses tumorigenesis in vivo. Nature Cell Biol. 11, 1451–1457.

    PubMed  CAS  Google Scholar 

  131. Johnson J., Lagowski J., Sundberg A., Lawson S., Liu Y., Kulesz-Martin M. 2007. p73 loss triggers conversion to squamous cell carcinoma reversible upon reconstitution with TAp73α. Cancer Res. 67, 7723–7730.

    PubMed  CAS  Google Scholar 

  132. Negrini S., Gorgoulis V.G., Halazonetis T.D. 2010. Genomic instability: An evolving hallmark of cancer. Nature Rev. Mol. Cell Biol. 11, 220–228.

    CAS  Google Scholar 

  133. Talos F., Nemajerova A., Flores E.R., Petrenko O., Moll U.M. 2007. p73 suppresses polyploidy and aneuploidy in the absence of functional p53. Mol. Cell. 27, 647–659.

    PubMed  CAS  Google Scholar 

  134. Tomasini R., Tsuchihara K., Tsuda C., Lau S.K., Wilhelm M., Ruffini A., Tsao M.S., Iovanna J.L., Jurisicova A., Melino G., Mak T.W. 2009. TAp73 regulates the spindle assembly checkpoint by modulating BubR1 activity. Proc. Natl. Acad. Sci. U.S.A. 106, 797–802.

    PubMed  CAS  Google Scholar 

  135. Adorno M., Cordenonsi M., Montagner M., Dupont S., Wong C., Hann B., Solari A., Bobisse S., Rondina M.B., Guzzardo V., Parenti A.R., Rosato A., Bicciato S., Balmain A., Piccolo S. 2009. A Mutant-p53/Smad complex opposes p63 to empower TGFβ-induced metastasis. Cell. 137, 87–98.

    PubMed  CAS  Google Scholar 

  136. Petrenko O., Zaika A., Moll U.M. 2003. ΔNp73 facilitates cell immortalization and cooperates with oncogenic Ras in cellular transformation in vivo. Mol. Cell Biol. 23, 5540–5555.

    PubMed  CAS  Google Scholar 

  137. Tannapfel A., John K., Mise N., Schmidt A., Buhlmann S., Ibrahim S.M., Putzer B.M. 2008. Autonomous growth and hepatocarcinogenesis in transgenic mice expressing the p53 family inhibitor DNp73. Carcinogenesis. 29, 211–218.

    PubMed  CAS  Google Scholar 

  138. Vella V., Puppin C., Damante G., Vigneri R., Sanfilippo M., Vigneri P., Tell G., Frasca F. 2009. ΔNp73α inhibits PTEN expression in thyroid cancer cells. Int. J. Cancer. 124, 2539–2548

    PubMed  CAS  Google Scholar 

  139. Vilgelm A.E., Hong S.M., Washington M.K., Wei J., Chen H., El-Rifai W., Zaika A. 2010. Characterization of ΔNp73 expression and regulation in gastric and esophageal tumors. Oncogene. 29, 5861–5868.

    PubMed  CAS  Google Scholar 

  140. Casciano I., Mazzocco K., Boni L., Pagnan G., Banelli B., Allemanni G., Ponzoni M., Tonini G.P., Romani M. 2002. Expression of ΔNp73 is a molecular marker for adverse outcome in neuroblastoma patients. Cell Death Differ. 9, 246–251.

    PubMed  CAS  Google Scholar 

  141. Uramoto H., Sugio K., Oyama T., Nakata S., Ono K., Morita M., Funa K., Yasumoto K. 2004. Expression of ΔNp73 predicts poor prognosis in lung cancer. Clin. Cancer Res. 10, 6905–6911.

    PubMed  CAS  Google Scholar 

  142. Muller M., Schilling T., Sayan A.E., Kairat A., Lorenz K., Schulze-Bergkamen H., Oren M., Koch A., Tannapfel A., Stremmel W., Melino G., Krammer P.H. 2005. TAp73/ΔNp73 influences apoptotic response, chemosensitivity and prognosis in hepatocellular carcinoma. Cell Death Differ. 12, 1564–1577.

    PubMed  CAS  Google Scholar 

  143. Liu S.S., Chan K.Y., Cheung A.N., Liao X.Y., Leung T.W., Ngan H.Y. 2006. Expression of ΔNp73 and TAp73α independently associated with radiosensitivities and prognoses in cervical squamous cell carcinoma. Clin. Cancer Res. 12, 3922–3927

    PubMed  CAS  Google Scholar 

  144. Concin N., Hofstetter G., Berger A., Gehmacher A., Reimer D., Watrowski R., Tong D., Schuster E., Hefler L., Heim K., Mueller-Holzner E., Marth C., Moll U.M., Zeimet A.G., Zeillinger R. 2005. Clinical relevance of dominant-negative p73 isoforms for responsiveness to chemotherapy and survival in ovarian cancer: Evidence for a crucial p53-p73 cross-talk in vivo. Clin. Cancer Res. 11, 8372–8383.

    PubMed  CAS  Google Scholar 

  145. Meier M., den Boer M.L., Meijerink J.P., Broekhuis M.J., Passier M.M., van Wering E.R., Janka-Schaub G.E., Pieters R. 2006. Differential expression of p73 isoforms in relation to drug resistance in childhood T-lineage acute lymphoblastic leukaemia. Leukemia. 20, 1377–1384.

    PubMed  CAS  Google Scholar 

  146. Zaika A.I., El-Rifai W. 2006. The role of p53 protein family in gastrointestinal malignancies. Cell Death Differ. 13, 935–940.

    PubMed  CAS  Google Scholar 

  147. Stiewe T., Tuve S., Peter M., Tannapfel A., Elmaagacli A.H., Putzer B.M. 2004. Quantitative TP73 transcript analysis in hepatocellular carcinomas. Clin. Cancer Res. 10, 626–633.

    PubMed  CAS  Google Scholar 

  148. Lucena-Araujo A.R., Panepucci R.A., dos Santos G.A., Jacomo R.H., Santana-Lemos B.A., Lima A.S., Garcia A.B., Araujo A.G., Falcao R.P., Rego E.M. 2008. The expression of ΔNTP73, TATP73 and TP53 genes in acute myeloid leukaemia is associated with recurrent cytogenetic abnormalities and in vitro susceptibility to cytarabine cytotoxicity. Br. J. Haematol. 142, 74–78.

    PubMed  CAS  Google Scholar 

  149. Rocco J.W., Leong C.O., Kuperwasser N., DeYoung M.P., Ellisen L.W. 2006. p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis. Cancer Cell. 9, 45–56.

    PubMed  CAS  Google Scholar 

  150. DeYoung M.P., Johannessen C.M., Leong C.O., Faquin W., Rocco J.W., Ellisen L.W. 2006. Tumor-specific p73 up-regulation mediates p63 dependence in squamous cell carcinoma. Cancer Res. 66, 9362–9368.

    PubMed  CAS  Google Scholar 

  151. Leong C.O., Vidnovic N., DeYoung M.P., Sgroi D., Ellisen L.W. 2007. The p63/p73 network mediates chemosensitivity to cisplatin in a biologically defined subset of primary breast cancers. J. Clin. Invest. 117, 1370–1380.

    PubMed  CAS  Google Scholar 

  152. Strano S., Fontemaggi G., Costanzo A., Rizzo M.G., Monti O., Baccarini A., Del Sal G., Levrero M., Sacchi A., Oren M., Blandino G. 2002. Physical interaction with human tumor-derived p53 mutants inhibits p63 activities. J. Biol. Chem. 277, 18817–18826.

    PubMed  CAS  Google Scholar 

  153. Di Como C.J., Gaiddon C., Prives C. 1999. p73 function is inhibited by tumor-derived p53 mutants in mammalian cells. Mol. Cell Biol. 19, 1438–1449.

    PubMed  Google Scholar 

  154. Gaiddon C., Lokshin M., Ahn J., Zhang T., Prives C. 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, 1874–1887.

    PubMed  CAS  Google Scholar 

  155. Schilling T., Kairat A., Melino G., Krammer P.H., Stremmel W., Oren M., Muller M. 2010. Interference with the p53 family network contributes to the gain of oncogenic function of mutant p53 in hepatocellular carcinoma. Biochem. Biophys. Res. Commun. 394, 817–823.

    PubMed  CAS  Google Scholar 

  156. Lang G.A., Iwakuma T., Suh Y.A., Liu G., Rao V.A., Parant J.M., Valentin-Vega Y.A., Terzian T., Caldwell L.C., Strong L.C., El-Naggar A.K., Lozano G. 2004. Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome. Cell. 119, 861–872.

    PubMed  CAS  Google Scholar 

  157. Li Y., Prives C. 2007. Are interactions with p63 and p73 involved in mutant p53 gain of oncogenic function? Oncogene. 26, 2220–2225.

    PubMed  CAS  Google Scholar 

  158. Wang S., El-Deiry W. S. 2006. p73 or p53 directly regulates human p53 transcription to maintain cell cycle checkpoints. Cancer Res. 66, 6982–6989.

    PubMed  CAS  Google Scholar 

  159. Chen X., Zheng Y., Zhu J., Jiang J., Wang J. 2001. p73 is transcriptionally regulated by DNA damage, p53, and p73. Oncogene. 20, 769–774.

    PubMed  CAS  Google Scholar 

  160. Wang J., Liu Y.X., Hande M.P., Wong A.C., Jin Y.J., Yin Y. 2007. TAp73 is a downstream target of p53 in controlling the cellular defense against stress. J. Biol. Chem. 282, 29152–29162.

    PubMed  CAS  Google Scholar 

  161. Grob T.J., Novak U., Maisse C., Barcaroli D., Luthi A.U., Pirnia F., Hugli B., Graber H.U., De Laurenzi V., Fey M.F., Melino G., Tobler A. 2001. Human ΔNp73 regulates a dominant negative feedback loop for TAp73 and p53. Cell Death Differ. 8, 1213–1223.

    PubMed  CAS  Google Scholar 

  162. Kartasheva N.N., Contente A., Lenz-Stoppler C., Roth J., Dobbelstein M. 2002. p53 induces the expression of its antagonist p73ΔN, establishing an autoregulatory feedback loop. Oncogene. 21, 4715–4727.

    PubMed  CAS  Google Scholar 

  163. Lanza M., Marinari B., Papoutsaki M., Giustizieri M.L., D’Alessandra Y., Chimenti S., Guerrini L., Costanzo A. 2006. Cross-talks in the p53 family: ΔNp63 is an antiapoptotic target for ΔNp73α and p53 gain-of-function mutants. Cell Cycle., 5, 1996–200

    PubMed  CAS  Google Scholar 

  164. Johnson J., Lagowski J., Lawson S., Liu Y., Kulesz-Martin M. 2007. p73 expression modulates p63 and Mdm2 protein presence in complex with p53 family-specific DNA target sequence in squamous cell carcinogenesis. Oncogene. 27, 2780–2787.

    PubMed  Google Scholar 

  165. Goldschneider D., Blanc E., Raguenez G., Barrois M., Legrand A., Le Roux G., Haddada H., Benard J., Douc-Rasy S. 2004. Differential response of p53 target genes to p73 overexpression in SH-SY5Y neuroblastoma cell line. J. Cell. Sci. 117, 293–301.

    PubMed  CAS  Google Scholar 

  166. Vilgelm A.E., Washington M.K., Wei J., Chen H., Prassolov V.S., Zaika A.I. 2010. Interactions of the p53 protein family in cellular stress response in gastrointestinal tumors. Mol. Cancer Ther. 9, 693–705.

    PubMed  CAS  Google Scholar 

  167. Cui R., Nguyen T.T., Taube J.H., Stratton S.A., Feuerman M.H., Barton M. C. 2005. Family members p53 and p73 act together in chromatin modification and direct repression of α-fetoprotein transcription. J. Biol. Chem. 280, 39152–39160.

    PubMed  CAS  Google Scholar 

  168. Yang A., Zhu Z., Kettenbach A., Kapranov P., McKeon F., Gingeras T.R., Struhl K. 2010. Genome-wide mapping indicates that p73 and p63 co-occupy target sites and have similar dna-binding profiles in vivo. PLoS One. 5, e11572.

    PubMed  Google Scholar 

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  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia

    A. E. Vilgelm & V. S. Prassolov

  2. Department of Surgery, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA

    A. E. Vilgelm & A. I. Zaika

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Original Russian Text © A.E. Vilgelm, A.I. Zaika, V.S. Prassolov, 2011, published in Molekulyarnaya Biologiya, 2011, Vol. 45, No. 1, pp. 180–197.

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Vilgelm, A.E., Zaika, A.I. & Prassolov, V.S. Coordinated interaction of multifunctional members of the p53 family determines many key processes in multicellular organisms. Mol Biol 45, 156–171 (2011). https://doi.org/10.1134/S002689331101016X

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