INSERM, U848, F-94805 Villejuif, France.
Curr Opin Cell Biol. 2010 Apr;22(2):181-5. doi: 10.1016/j.ceb.2009.12.001. Epub 2010 Jan 13.
Autophagy is an evolutionarily conserved catabolic pathway that is involved in numerous physiological processes and in multiple pathological conditions including cancer. Autophagy is regulated by an intricate network of signaling cascades that have not yet been entirely disentangled. Accumulating evidence indicates that p53, the best-characterized human tumor suppressor protein, can modulate autophagy in a dual fashion, depending on its subcellular localization. On the one hand, p53 functions as a nuclear transcription factor and transactivates proapoptotic, cell cycle-arresting and proautophagic genes. On the other hand, cytoplasmic p53 can operate at mitochondria to promote cell death and can repress autophagy via poorly characterized mechanisms. This review focuses on the recently discovered function of p53 as a master regulator of autophagy.
自噬是一种进化上保守的分解代谢途径，涉及多种生理过程和多种病理状况，包括癌症。自噬受到复杂的信号级联网络的调节，这些信号级联网络尚未完全理清。越来越多的证据表明，p53 是一种特征最明显的人类肿瘤抑制蛋白，它可以通过其亚细胞定位以双重方式调节自噬。一方面，p53 作为核转录因子发挥作用，并反式激活促凋亡、细胞周期停滞和促自噬基因。另一方面，细胞质 p53 可以在线粒体上发挥作用，促进细胞死亡，并通过尚未完全描述的机制抑制自噬。这篇综述重点介绍了 p53 作为自噬主调节因子的最新发现功能。
