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2004年2月13日
生物谷报道本周Science发文证实了p53直接介导bax导致线粒体膜通透性改变和凋亡。这是细胞凋亡研究中一项重要进展，了解bcl-2家族致凋亡的机理。
Direct Activation of Bax by p53 Mediates Mitochondrial Membrane Permeabilization and Apoptosis
Jerry E. Chipuk,1 Tomomi Kuwana,1 Lisa Bouchier-Hayes,1 Nathalie M. Droin,1 Donald D. Newmeyer,1 Martin Schuler,2 Douglas R. Green1*
The tumor suppressor p53 exerts its anti-neoplastic activity primarily through the induction of apoptosis. We found that cytosolic localization of endogenous wild-type or trans-activation–deficient p53 was necessary and sufficient for apoptosis. p53 directly activated the proapoptotic Bcl-2protein Bax in the absence of other proteins to permeabilize mitochondria and engage the apoptotic program. p53 also released both proapoptotic multidomain proteins and BH3-only proteins [Proapoptotic Bcl-2family proteins that share only the third Bcl-2homology domain (BH3)] that were sequestered by Bcl-xL. The transcription-independent activation of Bax by p53 occurred with similar kinetics and concentrations to those produced by activated Bid. We propose that when p53 accumulates in the cytosol, it can function analogously to the BH3-only subset of proapoptotic Bcl-2proteins to activate Bax and trigger apoptosis.
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生物谷严正声明：转载生物谷文章请注明来自生物谷
Direct Activation of Bax by p53 Mediates Mitochondrial Membrane Permeabilization and Apoptosis
Jerry E. Chipuk,1 Tomomi Kuwana,1 Lisa Bouchier-Hayes,1 Nathalie M. Droin,1 Donald D. Newmeyer,1 Martin Schuler,2 Douglas R. Green1*
The tumor suppressor p53 exerts its anti-neoplastic activity primarily through the induction of apoptosis. We found that cytosolic localization of endogenous wild-type or trans-activation–deficient p53 was necessary and sufficient for apoptosis. p53 directly activated the proapoptotic Bcl-2protein Bax in the absence of other proteins to permeabilize mitochondria and engage the apoptotic program. p53 also released both proapoptotic multidomain proteins and BH3-only proteins [Proapoptotic Bcl-2family proteins that share only the third Bcl-2homology domain (BH3)] that were sequestered by Bcl-xL. The transcription-independent activation of Bax by p53 occurred with similar kinetics and concentrations to those produced by activated Bid. We propose that when p53 accumulates in the cytosol, it can function analogously to the BH3-only subset of proapoptotic Bcl-2proteins to activate Bax and trigger apoptosis.
Full Text of this Article
PDF Version of this Article
Supporting Online Material
生物谷严正声明：转载生物谷文章请注明来自生物谷