Peg3/Pw1 promotes p53-mediated apoptosis by inducing Bax translocation from cytosol to mitochondria

被引:169
作者
Deng, YB
Wu, XW [1 ]
机构
[1] Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
关键词
D O I
10.1073/pnas.97.22.12050
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:12050 / 12055
页数:6
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