Pietsch E C, Sykes S M, McMahon S B, Murphy M E
Division of Medical Sciences, Fox Chase Cancer Center, Philadelphia, PA 19107, USA.
Oncogene. 2008 Oct 27;27(50):6507-21. doi: 10.1038/onc.2008.315.
The p53 tumor suppressor continues to hold distinction as the most frequently mutated gene in human cancer. The ability of p53 to induce programmed cell death, or apoptosis, of cells exposed to environmental or oncogenic stress constitutes a major pathway whereby p53 exerts its tumor suppressor function. In the past decade, we have discovered that p53 is not alone in its mission to destroy damaged or aberrantly proliferating cells: it has two homologs, p63 and p73, that in various cellular contexts and stresses contribute to this process. In this review, the mechanisms whereby p53, and in some cases p63 and p73, induce apoptosis are discussed. Other reviews have focused more extensively on the contribution of individual p53-regulated genes to apoptosis induction by this protein, whereas in this review, we focus more on those factors that mediate the decision between growth arrest and apoptosis by p53, p63 and p73, and on the post-translational modifications and protein-protein interactions that influence this decision.
p53肿瘤抑制因子仍是人类癌症中最常发生突变的基因。p53能够诱导接触环境或致癌应激的细胞发生程序性细胞死亡（即凋亡），这是p53发挥其肿瘤抑制功能的主要途径。在过去十年中，我们发现p53在破坏受损或异常增殖细胞的过程中并非独自发挥作用：它有两个同源物p63和p73，在各种细胞环境和应激条件下，它们也参与这一过程。在这篇综述中，我们将讨论p53以及某些情况下p63和p73诱导凋亡的机制。其他综述更广泛地关注了单个p53调控基因对该蛋白诱导凋亡的贡献，而在本综述中，我们更多地关注那些介导p53、p63和p73在生长停滞和凋亡之间做出决定的因素，以及影响这一决定的翻译后修饰和蛋白质-蛋白质相互作用。
