The dark side of a tumor suppressor:: anti-apoptotic p53

被引:152
作者
Janicke, R. U. [1 ]
Sohn, D. [1 ]
Schulze-Osthoff, K. [1 ]
机构
[1] Univ Dusseldorf, Inst Mol Med, D-40225 Dusseldorf, Germany
关键词
apoptosis; DNA repair; oxidative stress; survival pathways; transcription factor; tumorigenesis;
D O I
10.1038/cdd.2008.33
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Depending on multiple factors DNA damage leads either to cell cycle arrest or apoptosis. One of the main players deciding the fate of a cell is the tumor suppressor p53 that modulates these responses in a transcription-dependent and -independent manner. Over the past few years, however, strong evidence accumulated that p53 engages also powerful pro-survival pathways by transcriptionally activating a multitude of genes whose products efficiently counteract apoptosis. Our review summarizes the current knowledge concerning approximately forty p53-regulated proteins that exert their anti-apoptotic potential by interfering with diverse cellular processes. These activities are surely essential for normal development and maintenance of a healthy organism, but may easily turn into the dark side of the tumor suppressor p53 contributing to tumorigenesis.
引用
收藏
页码:959 / 976
页数:18
相关论文
共 173 条
[31]  
DEB SP, 1994, ONCOGENE, V9, P1341
[32]   Downregulation of 14-3-3σ prevents clonal evolution and leads to immortalization of primary human keratinocytes [J].
Dellambra, E ;
Golisano, O ;
Bondanza, S ;
Siviero, E ;
Lacal, P ;
Molinari, M ;
D'Atri, S ;
De Luca, M .
JOURNAL OF CELL BIOLOGY, 2000, 149 (05) :1117-1129
[33]   GAIN OF FUNCTION MUTATIONS IN P53 [J].
DITTMER, D ;
PATI, S ;
ZAMBETTI, G ;
CHU, S ;
TERESKY, AK ;
MOORE, M ;
FINLAY, C ;
LEVINE, AJ .
NATURE GENETICS, 1993, 4 (01) :42-46
[34]  
Donald SP, 2001, CANCER RES, V61, P1810
[35]   COP1, the negative regulator of p53, is overexpressed in breast and ovarian adenocarcinomas [J].
Dornan, D ;
Bheddah, S ;
Newton, K ;
Ince, W ;
Frantz, GD ;
Dowd, P ;
Koeppen, H ;
Dixit, VM ;
French, DM .
CANCER RESEARCH, 2004, 64 (20) :7226-7230
[36]   The ubiquitin ligase COP1 is a critical negative regulator of p53 [J].
Dornan, D ;
Wertz, I ;
Shimizu, H ;
Arnott, D ;
Frantz, GD ;
Dowd, P ;
O' Rourke, K ;
Koeppen, H ;
Dixit, VM .
NATURE, 2004, 429 (6987) :86-92
[37]   ATM engages autodegradation of the E3 ubiquitin ligase COP1 after DNA damage [J].
Dornan, David ;
Shimizu, Harumi ;
Mah, Angie ;
Dudhela, Tanay ;
Eby, Michael ;
O'Rourke, Karen ;
Seshagiri, Somasekar ;
Dixit, Vishva M. .
SCIENCE, 2006, 313 (5790) :1122-1126
[38]   Unlocking the code of 14-3-3 [J].
Dougherty, MK ;
Morrison, DK .
JOURNAL OF CELL SCIENCE, 2004, 117 (10) :1875-1884
[39]   Reciprocal down-regulation of p53 and SOD2 gene expression -: implication in p53 mediated apoptosis [J].
Drane, P ;
Bravard, A ;
Bouvard, V ;
May, E .
ONCOGENE, 2001, 20 (04) :430-439
[40]   Polo-like kinases and oncogenesis [J].
Eckerdt, F ;
Yuan, JP ;
Strebhardt, K .
ONCOGENE, 2005, 24 (02) :267-276