Yonish-Rouach E, Choisy C, Deguin V, Breugnot C, May E
Laboratoire de Cancérogenèse Moléculaire, UMR 217, DRR, SDV, CEA, Fontenay aux-Roses, France.
Behring Inst Mitt. 1996 Oct(97):60-71.
The tumor suppressor gene p53 plays a major role in the protection of cells from DNA damage. Activation of the protein in response to irradiation or genotoxic agents, and possibly by other signals, results in growth arrest at the G1 phase of the cell cycle or in apoptosis. While it has been shown that the ability of p53 to function as a sequence-specific transcriptional activator is necessary for the induction of growth arrest, the mechanism of p53-mediated apoptosis is not clear yet. In the present report we summarize the results obtained by several groups concerning p53-mediated apoptotic pathway. We suggest that p53 may induce apoptosis via a complex network of interacting pathways, which may be transcriptionally dependent or independent, depending on external signals and on the cellular context. Whatever the mechanisms are, the outcome-cell death by apoptosis-is a key function of the tumor suppressor p53.
肿瘤抑制基因p53在保护细胞免受DNA损伤方面发挥着重要作用。该蛋白在受到辐射或基因毒性试剂刺激时被激活，也可能由其他信号激活，从而导致细胞周期在G1期停滞或引发细胞凋亡。虽然已经表明p53作为序列特异性转录激活因子发挥功能的能力对于诱导细胞生长停滞是必要的，但p53介导的细胞凋亡机制尚不清楚。在本报告中，我们总结了几个研究小组关于p53介导的凋亡途径所获得的结果。我们认为，p53可能通过一个相互作用途径的复杂网络诱导细胞凋亡，这可能取决于外部信号和细胞环境，是转录依赖性的或非依赖性的。无论机制如何，细胞凋亡导致的细胞死亡这一结果是肿瘤抑制因子p53的关键功能。
