Stress-induced p53 runs a direct mitochondrial death program - Its role in physiologic and pathophysiologic stress responses in vivo
Stress-induced p53 runs a direct mitochondrial death program - Its role in physiologic and pathophysiologic stress responses in vivo
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DOI：
10.4161/cc.3.12.1318
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发表时间：
2004-12-01
期刊：
影响因子：
4.3
通讯作者：
Moll, UM
中科院分区：
文献类型：
--
作者：
Erster, S;Moll, UM
现在已经确定，在培养的永生化和转化细胞中，一部分应激诱导的wtp53蛋白快速易位到线粒体。线粒体p53与Bcl 2家族的抗凋亡蛋白在线粒体外膜处相互作用，导致膜透化，释放死亡效应物如细胞色素C和随后的快速凋亡。最近在动物和原代细胞中的一些研究强调了这种直接线粒体p53程序对体内整体p53介导的应激反应的意义和相关性。他们都支持这一直接途径的作用，在生理和病理生理反应的遗传毒性和缺氧的侮辱，并发生在这些组织中，p53在介导apotpotis，而不是细胞周期停滞中起着至关重要的作用。
It is now well established that a fraction of stress-induced wtp53 protein rapidly translocates to mitochondria in immortalized and transformed cells in culture. Mitochondrial p53 interacts with anti-apoptotic proteins of the Bcl 2 family at the outer mitochondrial membrane, resulting in membrane permeabilization, release of death effectors such as cytochrome C and subsequent rapid apoptosis. The significance and relevance of this direct mitochondrial p53 program to the overall p53-mediated stress response in vivo is underlined by a number of recent studies in animals and primary cells. They all support a role for this direct pathway in the physiologic and pathophysiologic response to genotoxic and hypoxic insults and occur precisely in those tissues where p53 plays a critical role in mediating apotpotis rather than cell cycle arrest.