Cellular and organismal ageing: Role of the p53 tumor suppressor protein in the induction of transient and terminal senescence

Journal of Cellular Biochemistry

Volumn 101, Issue 6, 2007, Pages 1355-1369

  Schmid, Gerald ^a,b   Kramer, Matthias P ^a   Maurer, Margarita ^a   Wandl, Stefanie ^a   Wȩsierska Ga̧dek, Józefa ^a,b  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b Vela pharm Entwicklung u Laboranalytik GmbH   (Austria)

Author keywords

CDK inhibitors; Cell cycle; Cell cycle arrest; HIPK2; Mdm2; p53 isoforms; p53 stability; p53 ubiquitylation; PML

Indexed keywords

HISTONE DEACETYLASE; PROTEIN P44; PROTEIN P53; PROTEIN SRIT1; SOMATOMEDIN; TUMOR SUPPRESSOR PROTEIN; UNCLASSIFIED DRUG;

AGING; APOPTOSIS; ARTICLE; CAENORHABDITIS ELEGANS; CALORIC RESTRICTION; CELL AGING; DROSOPHILA MELANOGASTER; ENERGY METABOLISM; EVOLUTION; HUMAN; LIFESPAN; NONHUMAN; PRIORITY JOURNAL; SACCHAROMYCES CEREVISIAE;

AGING; ANIMALS; CARRIER PROTEINS; CELL AGING; CYCLIN-DEPENDENT KINASE INHIBITOR P16; ENZYME ACTIVATION; HUMANS; NEOPLASM PROTEINS; NEOPLASMS; NUCLEAR PROTEINS; PROTEIN ISOFORMS; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS C-MDM2; TRANSCRIPTION FACTORS; TUMOR SUPPRESSOR PROTEIN P53; TUMOR SUPPRESSOR PROTEINS; UBIQUITIN-PROTEIN LIGASES;

CAENORHABDITIS ELEGANS; DROSOPHILA MELANOGASTER; MUS; SACCHAROMYCES CEREVISIAE;

EID: 34547806596     PISSN: 07302312     EISSN: 10974644     Source Type: Journal    
DOI: 10.1002/jcb.21383     Document Type: Article

References (113)

1. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA. 2006. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337-342.
2. Beausejour CM, Campisi J. 2006. Ageing: Balancing regeneration and cancer. Nature 443:404-405.
3. Beausejour CM, Krtolica A, Galimi F, Narita M, Lowe SW, Yaswen P, Campisi J. 2003. Reversal of human cellular senescence: Roles of the p53 and p16 pathways. EMBO J 22:4212-4222.
4. Bernardi R, Scaglioni PP, Bergmann S, Horn HF, Vousden KH, Pandolfi PP. 2004. PML regulates p53 stability by sequestering Mdm2 to the nucleolus. Nat Cell Biol 6:665-672.
5. Bischof O, Kirsh O, Pearson M, Itahana K, Pelicci PG, Dejean A. 2002. Deconstructing PML-induced premature senescence. EMBO J 21:3358-3369.
6. Borden KL. 2002. Pondering the promyelocyte leukemia protein (PML) puzzle: Possible functions for PML nuclear bodies. Mol Cell Biol 22:5259-5269.
7. Burkle A, Beneke S, Muiras ML. 2004. Poly(ADP-ribosyl)ation and aging. Exp Gerontol 39:1599-1601.
8. Campisi J. 2001. Cellular senescence as a tumor-suppressor mechanism. Trends Cell Biol 11:S27-31.
9. Campisi J. 2005. Senescent cells, tumor suppression, and organismal aging: Good citizens, bad neighbors. Cell 120:513-522.
10. Clarke AR, Hollstein M. 2003. Mouse models with modified p53 sequences to study cancer and ageing. Cell Death Differ 10:443-450.
11. Courtois S, Verhaegh G, North S, Luciani MG, 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.
12. Dartnell L, Simeonidis E, Hubank M, Tsoka S, Bogle ID, Papageorgiou LG. 2005. Robustness of the p53 network and biological hackers. FEBS Lett 579:3037-3042.
13. de Stanchina E, Querido E, Narita M, Davuluri RV, Pandolfi PP, Ferbeyre G, Lowe SW. 2004. PML is a direct p53 target that modulates p53 effector functions. Mol Cell 13:523-535.
14. de The H, Lavau C, Marchio A, Chomienne C, Degos L, Dejean A. 1991. The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocyte leukemia encodes a functionally altered RAR. Cell 66:675-684.
15. DeLeo AB, Jay G, Appella E, Dubois GC, Law LW, Old LJ. 1979. Detection of a transformation-related antigen in chemically induced sarcomas and other transformed cells of the mouse. Proc Natl Acad Sci USA 76:2420-2424.
16. Donehower LA. 2002. Does p53 affect organismal aging? J Cell Physiol 192:23-33.
17. D'Orazi G, Cecchinelli B, Bruno T, Manni I, Higashimoto Y, Saito S, Gostissa M, Coen S, Marchetti A, Del Sal G, Piaggio G, Fanciulli M, Appella E, Soddu S. 2002. Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis. Nat Cell Biol 4:11-19.
18. Dornan D, Bheddah S, Newton K, Ince W, Frantz GD, Dowd P, Koeppen H, Dixit VM, French DM. 2004a. COP1, the negative regulator of p53, is overexpressed in breast and ovarian adenocarcinomas. Cancer Res 64:7226-7230.
19. Dornan D, Wertz I, Shimizu H, Arnott D, Frantz GD, Dowd P, O'Rourke K, Koeppen H, Dixit VM. 2004b. The ubiquitin ligase COP1 is a critical negative regulator of p53. Nature 429:86-92.
20. Duan W, Gao L, Druhan LJ, Zhu WG, Morrison C, Otterson GA, Villalona-Calero MA. 2004. Expression of Pirh2, a newly identified ubiquitin protein ligase, in lung cancer. J Natl Cancer Inst 96:1718-1721.
21. Duan W, Gao L, Wu X, Zhang Y, Otterson GA, Villalona-Calero MA. 2006. Differential response between the p53 ubiquitin-protein ligases Pirh2 and MdM2 following DNA damage in human cancer cells. Exp Cell Res 312:3370-3378.
22. Fang S, Jensen JP, Ludwig RL, Vousden KH, Weissman AM. 2000. Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J Biol Chem 275:8945-8951.
23. Ferbeyre G, de Stanchina E, Querido E, Baptiste N, Prives C, Lowe SW. 2000. PML is induced by oncogenic ras and promotes premature senescence. Genes Dev 14:2015-2027.
24. Fogal V, Gostissa M, Sandy P, Zacchi P, Sternsdorf T, Jensen K, Pandolfi PP, Will H, Schneider C, Del Sal G. 2000. Regulation of p53 activity in nuclear bodies by a specific PML isoform. EMBO J 19:6185-6195.
25. Gannon JV, Lane DP. 1991. Protein synthesis required to anchor a mutant p53 protein which is temperature-sensitive for nuclear transport. Nature 349:802-806.
26. Garcia-Cao I, Garcia-Cao M, Martin-Caballero J, Criado LM, Klatt P, Flores JM, Weill JC, Blasco MA, Serrano M. 2002. "Super p53" mice exhibit enhanced DNA damage response, are tumor resistant and age normally. EMBO J 21:6225-6235.
27. Gems D, Partridge L. 2001. Insulin/IGF signalling and ageing: Seeing the bigger picture. Curr Opin Genet Dev 11:287-292.
28. Gerstein AD, Phillips TJ, Rogers GS, Gilchrest BA. 1993. Wound healing and aging. Dermatol Clin 11:749-757.
29. Ghosh A, Stewart D, Matlashewski G. 2004. Regulation of human p53 activity and cell localization by alternative splicing. Mol Cell Biol 24:7987-7997.
30. Gottlieb S, Esposito RE. 1989. A new role for a yeast transcriptional silencer gene, SIR2, in regulation of recombination in ribosomal DNA. Cell 56:771-776.
31. Grossman SR, Deato ME, Brignone C, Chan HM, Kung AL, Tagami H, Nakatani Y, Livingston DM. 2003. Polyubiquitination of p53 by a ubiquitin ligase activity of p300. Science 300:342-344.
32. Gu W, Roeder RG. 1997. Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 90:595-606.
33. Guarente L. 2000. Sir2 links chromatin silencing, metabolism, and aging. Genes Dev 14:1021-1026.
34. Guarente L, Kenyon C. 2000. Genetic pathways that regulate ageing in model organisms. Nature 408:255-262.
35. Guo A, Salomoni P, Luo J, Shih A, Zhong S, Gu W, Pandolfi PP. 2000. The function of PML in p53-dependent apoptosis. Nat Cell Biol 2:730-736.
36. Haider UG, Sorescu D, Griendling KK, Vollmar AM, Dirsch VM. 2003. Resveratrol increases serine15-phosphorylated but transcriptionally impaired p53 and induces a reversible DNA replication block in serum-activated vascular smooth muscle cells. Mol Pharmacol 63:925-932.
37. Haupt S, Berger M, Goldberg Z, Haupt Y. 2003. Apoptosis - the p53 network. J Cell Sci 116:4077-4085.
38. Hofmann TG, Moller A, Sirma H, Zentgraf H, Taya Y, Droge W, Will H, Schmitz ML. 2002. Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2. Nat Cell Biol 4:1-10.
39. Honda R, Yasuda H. 1999. Association of p19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53. EMBO J 18:22-27.
40. Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA. 2003. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425:191-196.
41. Janzen V, Forkert R, Fleming HE, Saito Y, Waring MT, Dombkowski DM, Cheng T, DePinho RA, Sharpless NE, Scadden DT. 2006. Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443:421-426.
42. Jones SN, Roe AE, Donehower LA, Bradley A. 1995. Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53. Nature 378:206-208.
43. Kaeberlein M, Rabinovitch PS. 2006. Medicine: Grapes versus gluttony. Nature 444:280-281.
44. Kaeberlein M, McVey M, Guarente L. 1999. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 13:2570-2580.
45. Kaeberlein M, Kirkland KT, Fields S, Kennedy BK. 2004. Sir2-independent life span extension by calorie restriction in yeast. PLoS Biol 2:E296.
46. Keyes WM, Mills AA. 2006. p63: A new link between senescence and aging. Cell Cycle 5:260-265.
47. Keyes WM, Wu Y, Vogel H, Guo X, Lowe SW, Mills AA. 2005. p63 deficiency activates a program of cellular senescence and leads to accelerated aging. Genes Dev 19:1986-1999.
48. Kim YA, Choi BT, Lee YT, Park DI, Rhee SH, Park KY, Choi YH. 2004. Resveratrol inhibits cell proliferation and induces apoptosis of human breast carcinoma MCF-7 cells. Oncol Rep 11:441-446.
49. Kohn KW. 1999. Molecular interaction map of the mammalian cell cycle control and DNA repair systems. Mol Biol Cell 10:2703-2734.
50. Kohn KW, Pommier Y. 2005. Molecular interaction map of the p53 and Mdm2 logic elements, which control the Off-On switch of p53 in response to DNA damage. Biochem Biophys Res Commun 331:816-827.
51. Krishnamurthy J, Ramsey MR, Ligon KL, Torrice C, Koh A, Bonner-Weir S, Sharpless NE. 2006. p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 443:453-457.
52. Kulikov R, Winter M, Blattner C. 2006. Binding of p53 to the central domain of Mdm2 is regulated by phosphorylation. J Biol Chem 281:28575-28583.
53. Kurki S, Latonen L, Laiho M. 2003. Cellular stress and DNA damage invoke temporally distinct Mdm2, p53 and PML complexes and damage-specific nuclear relocalization. J Cell Sci 116:3917-3925.
54. Lane DP, Crawford LV. 1979. T antigen is bound to a host protein in SV40-transformed cells. Nature 278:261-263.
55. Langley E, Pearson M, Faretta M, Bauer UM, Frye RA, Minucci S, Pelicci PG, Kouzarides T. 2002. Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J 21:2383-2396.
56. Lavigueur A, Maltby V, Mock D, Rossant J, Pawson T, Bernstein A. 1989. High incidence of lung, bone, and lymphoid tumors in transgenic mice overexpressing mutant alleles of the p53 oncogene. Mol Cell Biol 9:3982-3991.
57. Leng RP, Lin Y, Ma W, Wu H, Lemmers B, Chung S, Parant JM, Lozano G, Hakem R, Benchimol S. 2003. Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation. Cell 112:779-791.
58. Lin AW, Barradas M, Stone JC, van Aelst L, Serrano M, Lowe SW. 1998. Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling. Genes Dev 12:3008-3019.
59. Lin SJ, Defossez PA, Guarente L. 2000. Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289:2126-2128.
60. Linzer DI, Levine AJ. 1979. Characterization of a 54 K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell 17:43-52.
61. Logan IR, Sapountzi V, Gaughan L, Neal DE, Robson CN. 2004. Control of human PIRH2 protein stability: Involvement of TIP60 and the proteosome. J Biol Chem 279:11696-11704.
62. Louria-Hayon I, Grossman T, Sionov RV, Alsheich O, Pandolfi PP, Haupt Y. 2003. The promyelocyte leukemia protein protects p53 from Mdm2-mediated inhibition and degradation. J Biol Chem 278:33134-33141.
63. Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, Guarente L, Gu W. 2001. Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell 107:137-148.
64. Ma J, Martin JD, Zhang H, Auger KR, Ho TF, Kirkpatrick RB, Grooms MH, Johanson KO, Tummino PJ, Copeland RA, Lai Z. 2006. A second p53 binding site in the central domain of Mdm2 is essential for p53 ubiquitination. Biochemistry 45:9238-9245.
65. Maier B, Gluba W, Bernier B, Turner T, Mohammad K, Guise T, Sutherland A, Thorner M, Scrable H. 2004. Modulation of mammalian life span by the short isoform of p53. Genes Dev 18:306-319.
66. Matlashewski G, Pim D, Banks L, Crawford L. 1987. Alternative splicing of human p53 transcripts. Oncogene Res 1:77-85.
67. Mayo LD, Donner DB. 2001. A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc Natl Acad Sci USA 98:11598-11603.
68. Meek DW, Knippschild U. 2003. Posttranslational modification of M DM2. Mol Cancer Res 1:1017-1026.
69. Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P, Moll UM. 2003. p53 has a direct apoptogenic role at the mitochondria. Mol Cell 11:577-590.
70. Moller A, Sirma H, Hofmann TG, Rueffer S, Klimczak E, Droge W, Will H, Schmitz ML. 2003. PML is required for homeodomain-interacting protein kinase 2 (HIPK2)-mediated p53 phosphorylation and cell cycle arrest but is dispensable for the formation of HIPK domains. Cancer Res 63:4310-4314.
71. Molofsky AV, Slutsky SG, Joseph NM, He S, Pardal R, Krishnamurthy J, Sharpless NE, Morrison SJ. 2006. Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443:448-452.
72. Montes de Oca Luna R, Wagner DS, Lozano G, 1995. Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature 378:203-206.
73. Mortimer RK, Johnston JR. 1959. Life span of individual yeast cells. Nature 183:1751-1752.
74. Mosner J, Mummenbrauer T, Bauer C, Sczakiel G, Grosse F, Deppert W. 1995. Negative feedback regulation of wild-type p53 biosynthesis. EMBO J 14:4442-4449.
75. Mowat M, Cheng A, Kimura N, Bernstein A, Benchimol S. 1985. Rearrangements of the cellular p53 gene in erythroleukaemic cells transformed by Friend virus. Nature 314:633-636.
76. Narayanan BA, Narayanan NK, Stoner GD, Bullock BP. 2002. Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants. Life Sci 70:1821-1839.
77. Narayanan BA, Narayanan NK, Re GG, Nixon DW. 2003. Differential expression of genes induced by resveratrol in LNCaP cells: P53-mediated molecular targets. Int J Cancer 104:204-212.
78. Nemoto S, Fergusson MM, Finkel T. 2004. Nutrient availability regulates SIRT1 through a forkhead-dependent pathway. Science 306:2105-2108.
79. Oda K, Arakawa H, Tanaka T, Matsuda K, Tanikawa C, Mori T, Nishimori H, Tamai K, Tokino T, Nakamura Y, Taya Y. 2000. p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53. Cell 102:849-862.
80. Oh W, Lee EW, Sung YH, Yang MR, Ghim J, Lee HW, Song J. 2006. Jab1 induces the cytoplasmic localization and degradation of p53 in coordination with Hdm2. J Biol Chem 281:17457-17465.
81. Oliner JD, Kinzler KW, Meltzer PS, George DL, Vogelstein B. 1992. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 358:80-83.
82. Papazoglu C, Mills AA. 2007. p53: At the crossroad between cancer and ageing. J Pathol 211:124-133.
83. Pearson M, Carbone R, Sebastiani C, Cioce M, Fagioli M, Saito S, Higashimoto Y, Appella E, Minucci S, Pandolfi PP, Pelicci PG. 2000. PML regulates p53 acetylation and premature senescence induced by oncogenic Ras. Nature 406:207-210.
84. Piazza F, Gurrieri C, Pandolfi PP. 2001. The theory of APL. Oncogene 20:7216-7222.
85. Reyes JC. 2001. PML and COP1 - two proteins with much in common. Trends Biochem Sci 26:18-20.
86. Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, Riganelli D, Zanaria E, Messali S, Cainarca S, Guffanti A, Minucci S, Pelicci PG, Ballabio A. 2001. The tripartite motif family identifies cell compartments. EMBO J 20:2140-2151.
87. Richardson A, Liu F, Adamo ML, Van Remmen H, Nelson JF. 2004. The role of insulin and insulin-like growth factor-I in mammalian ageing. Best Pract Res Clin Endocrinol Metab 18:393-406.
88. Ries S, Biederer C, Woods D, Shifman O, Shirasawa S, Sasazuki T, McMahon M, Oren M, McCormick F. 2000. Opposing effects of Ras on p53: Transcriptional activation of mdm2 and induction of p19ARF. Cell 103:321-330.
89. Roovers K, Assoian RK. 2000. Integrating the MAP kinase signal into the G1 phase cell cycle machinery. Bioessays 22:818-826.
90. Rovinski B, Benchimol S. 1988. Immortalization of rat embryo fibroblasts by the cellular p53 oncogene. Oncogene 2:445-452.
91. Scrable H, Sasaki T, Maier B. 2005. DeltaNp53 or p44: Priming the p53 pump. Int J Biochem Cell Biol 37:913-919.
92. Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW. 1997. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88:593-602.
93. She QB, Bode AM, Ma WY, Chen NY, Dong Z. 2001. Resveratrol-induced activation of p53 and apoptosis is mediated by extracellular-signal-regulated protein kinases and p38 kinase. Cancer Res 61:1604-1610.
94. Sinclair DA, Guarente L. 1997. Extrachromosomal rDNA circles - a cause of aging in yeast. Cell 91:1033-1042.
95. Stuurman N, Floore A, Middelkoop E, van Driel R, de Jong L. 1997. PML shuttles between nuclear bodies and the cytoplasm. Cell Mol Biol Lett 2:137-150.
96. Tomoda K, Yoneda-Kato N, Fukumoto A, Yamanaka S, Kato JY. 2004. Multiple functions of Jab1 are required for early embryonic development and growth potential in mice. J Biol Chem 279:43013-43018.
97. Tyner SD, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H, Lu X, Soron G, Cooper B, Brayton C, Hee Park S, Thompson T, Karsenty G, Bradley A, Donehower LA. 2002. p53 mutant mice that display early ageing-associated phenotypes. Nature 415:45-53.
98. Unger T, Juven-Gershon T, Moallem E, Berger M, Vogt Sionov R, Lozano G, Oren M, Haupt Y. 1999. Critical role for Ser20 of human p53 in the negative regulation of p53 by Mdm2. EMBO J 18:1805-1814.
99. Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye EA, Pandita TK, Guarente L, Weinberg RA. 2001. hSIR2-(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 107:149-159.
100. Wei X, Yu ZK, Ramalingam A, Grossman SR, Yu JH, Bloch DB, Maki CG. 2003. Physical and functional interactions between PML and M DM2. J Biol Chem 278:29288-29297.
101. Wesierska-Gadek J, Schmid G. 2005. The subcellular distribution of the p53 tumour suppressor, and organismal ageing. Cell Mol Biol Lett 10:439-453.
102. Wesierska-Gadek J, Gueorguieva M, Horky M. 2005a. Roscovitine-induced up-regulation of p53AIP1 protein precedes the onset of apoptosis in human MCF-7 breast cancer cells. Mol Cancer Ther 4:113-124.
103. Wesierska-Gadek J, Ranftler C, Schmid G. 2005b. Physiological ageing: Role of p53 and PARP-1 tumor suppressors in the regulation of terminal senescence. J Physiol Pharmacol 56 (Suppl 2):77-88.
104. Wesierska-Gadek J, Wojciechowski J, Ranftler C, Schmid G. 2005c. Role of p53 tumor suppressor in ageing: Regulation of transient cell cycle arrest and terminal senescence. J Physiol Pharmacol 56:15-28.
105. Wesierska-Gadek J, Schmitz ML, Ranftler C. 2007. Roscovitine-activated HIP2 kinase induces phosphorylation of wt p53 at Ser-46 in human MCF-7 breast cancer cells. J Cell Biochem 100:865-874.
106. Wojciechowski J, Horky M, Gueorguieva M, Wesierska-Gadek J. 2003. Rapid onset of nucleolar disintegration preceding cell cycle arrest in roscovitine-induced apoptosis of human MCF-7 breast cancer cells. Int J Cancer 106:486-495.
107. Wu C, Miloslavskaya I, Demontis S, Maestro R, Galaktionov K. 2004. Regulation of cellular response to oncogenic and oxidative stress by Seladin-1. Nature 432:640-645.
108. Wu CH, Apweiler R, Bairoch A, Natale DA, Barker WC, Boeckmann B, Ferro S, Gasteiger E, Huang H, Lopez R, Magrane M, Martin MJ, Mazumder R, O'Donovan C, Redaschi N, Suzek B. 2006. The Universal Protein Resource (UniProt): an expanding universe of protein information. Nucleic Acids Res 34:D187-191.
109. Yi C, Deng XW. 2005. COP1 - from plant photomorphogenesis to mammalian tumorigenesis. Trends Cell Biol 15:618-625.
110. Yin Y, Stephen CW, Luciani MG, Fahraeus R. 2002. p53 Stability and activity is regulated by Mdm2-mediated induction of alternative p53 translation products. Nat Cell Biol 4:462-467.
111. Yu GW, Rudiger S, Veprintsev D, Freund S, Fernandez-Fernandez MR, Fersht AR. 2006. The central region of HDM2 provides a second binding site for p53. Proc Natl Acad Sci USA 103:1227-1232.
112. Zhang S, Cao HJ, Davis FB, Tang HY, Davis PJ, Lin HY. 2004. Oestrogen inhibits resveratrol-induced post-translational modification of p53 and apoptosis in breast cancer cells. Br J Cancer 91:178-185.
113. Zhu J, Woods D, McMahon M, Bishop JM. 1998. Senescence of human fibroblasts induced by oncogenic Raf. Genes Dev 12:2997-3007.