Peg3/Pw1 promotes p53-mediated apoptosis by inducing Bax translocation from cytosol to mitochondria
Peg3/Pw1 promotes p53-mediated apoptosis by inducing Bax translocation from cytosol to mitochondria
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DOI：
10.1073/pnas.97.22.12050
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发表时间：
2000-10-24
影响因子：
11.1
通讯作者：
Wu, XW
中科院分区：
文献类型：
--
作者：
Deng, YB;Wu, XW
线粒体被认为在p53介导的细胞凋亡中起核心作用。然而，导致线粒体的信号转导途径仍不清楚。在这里，我们报告说，Bax蛋白从胞质到线粒体的易位是p53诱导的细胞凋亡所必需的。胞浆Bax不能诱导细胞凋亡，阻断Bax易位抑制细胞死亡。Bcl-2的表达阻断了细胞色素c的释放和细胞凋亡，但对Bax易位没有影响，表明Bax易位作用于Bcl-2的上游。我们进一步证明Peg 3/Pw 1，一个在p53介导的细胞死亡过程中上调的蛋白，诱导Bax易位而不依赖于凋亡。结果表明，Bax易位是p53介导的细胞凋亡中的一个重要调控步骤，Peg 3/Pw 1作为p53下游的调节剂调节Bax在细胞中的再分布。因此，有利于细胞决定凋亡超过生长停滞后p53诱导。
Mitochondria is believed to play a central role in p53-mediated apoptosis. However, the signal transduction pathways leading to mitochondria remain unclear. Here, we report that translocation of Bax protein from cytosol to mitochondria is required for p53-induced apoptosis. Cytosolic Bax is unable to induce apoptosis, and blocking Bax translocation inhibits cell death. Expression of Bcl-2 blocks cytochrome c release and apoptosis but has no effect on Bax translocation, suggesting that Bax translocation acts upstream of Bcl-2. We:further demonstrate that Peg3/Pw1, a protein up-regulated in p53-mediated cell death process, induces Bax translocation independent of apoptosis. The results suggest that Bax translocation represents an important regulatory step in p53-mediated apoptosis, and Peg3/Pw1 functions as a modulator downstream of p53 to regulate Bax redistribution in the cells. Thus favoring the cellular decision toward apoptosis over growth arrest following p53 induction.