Yonish-Rouach E
Laboratoire de Cancérogenèse Moléculaire, UMR 217 du CNRS/CEA, DRR-DSV, Fontenay-aux-Roses, France.
Pathol Biol (Paris). 1997 Dec;45(10):815-23.
The tumor suppressor gene p53 plays a major role in the protection of cell 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. It appears that under some conditions activation of the G1 checkpoint will prevent apoptosis, but cellular environment may alter the result of p53 activation towards cell death. p53 may also directly induce apoptosis through several pathways, which may be transcriptionally dependent or independent. The outcome--a G1 arrest or apoptosis--will depend on a complex network of regulatory signals.
肿瘤抑制基因p53在保护细胞免受DNA损伤方面发挥着主要作用。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期停滞或发生凋亡。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是诱导生长停滞所必需的,但p53介导的凋亡机制尚不清楚。似乎在某些情况下,G1检查点的激活会阻止凋亡,但细胞环境可能会改变p53激活导致细胞死亡的结果。p53也可能通过几种途径直接诱导凋亡,这些途径可能是转录依赖性的或非依赖性的。结果——G1期停滞或凋亡——将取决于一个复杂的调节信号网络。