Mitochondrial localization of the low level p53 protein in proliferative cells
Mitochondrial localization of the low level p53 protein in proliferative cells
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DOI：
10.1016/j.bbrc.2009.07.111
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发表时间：
2009-10-02
影响因子：
3.1
通讯作者：
Vayssiere, Jean-Luc
中科院分区：
文献类型：
--
作者：
Ferecatu, Ioana;Bergeaud, Marie;Vayssiere, Jean-Luc
P53蛋白通过转录依赖和不依赖的机制诱导细胞周期阻滞或凋亡，在抑制肿瘤发生中发挥核心作用。新出现的出版物表明，应激后，一部分p53易位到线粒体，诱导细胞色素c释放和细胞凋亡。然而，在非应激条件下p53的定位在很大程度上仍未被探索。在这里，我们发现p53在没有凋亡刺激的情况下定位于线粒体，当细胞增殖时，定位在各种细胞类型（啮齿动物和人类）中观察到。这也得到了脱细胞试验的支持，其中p53与从大鼠肝脏分离的线粒体强烈结合。此外，线粒体亚分离研究和线粒体p53的碱性处理表明，大部分线粒体p53存在于膜室中。最后，我们确定了线粒体外膜蛋白VDAC，作为非应激/增殖细胞中p53的推定伴侣。(C) 2009爱思唯尔公司版权所有。
p53 protein plays a central role in suppressing tumorigenesis by inducing cell cycle arrest or apoptosis through transcription-dependent and -independent mechanisms. Emerging publications suggest that following stress, a fraction of p53 translocates to mitochondria to induce cytochrome c release and apoptosis. However, the localization of p53 under unstressed conditions remains largely unexplored. Here we show that p53 is localized at mitochondria in absence of apoptotic stimuli, when cells are proliferating, localization observed in various cell types (rodent and human). This is also supported by acellular assays in which p53 bind strongly to mitochondria isolated from rat liver. Furthermore, the mitochondria sub-fractionation study and the alkaline treatment of the mitochondrial p53 revealed that the majority of mitochondrial p53 is present in the membranous compartments. Finally, we identified VDAC, a protein of the mitochondrial outer-membrane, as a putative partner of p53 in unstressed/proliferative cells. (C) 2009 Elsevier Inc. All rights reserved.