| A natural compound elevates expression of Bim that interacts with Bcl-2 converting the anti-apoptotic protein to a pro-apoptotic Bax-like molecule. | |
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MedLine Citation:
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PMID: 22065578 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Overwhelming evidence indicates that Bax and Bak are indispensable for mediating cytochrome c release from mitochondria during apoptosis. Here we report a Bax/Bak-independent mechanism of cytochrome c release and apoptosis. We identified a natural diterpenoid compound that induced apoptosis in bax/bak double knockout murine embryonic fibroblasts, and substantially reduced the tumor growth from these cells implanted in mice. Treatment with the compound significantly increased expression of Bim, which migrated to mitochondria, altering the conformation of and forming oligomers with resident Bcl-2 to induce cytochrome c release and caspase activation. Importantly, purified Bim and Bcl-2 proteins cooperated to permeabilize a model mitochondrial outer membrane, which was accompanied by oligomerization of these proteins and deeply embedding Bcl-2 in the membrane. Therefore, the diterpenoid compound induces a structural and functional conversion of Bcl-2 through Bim to permeabilize the mitochondrial outer membrane thereby inducing apoptosis independent of Bax and Bak. Since Bcl-2 family proteins play important roles in cancer development and relapse, this novel cell death mechanism can be explored for developing more effective anti-cancer therapeutics. |
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Authors:
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Lixia Zhao; Feng He; Haiyang Liu; Yushan Zhu; Weili Tian; Ping Gao; Hongping He; Wen Yue; Xiaobo Lei; Biyun Ni; Xiaohui Wang; Haijing Jin; Xiaojiang Hao; Jialing Lin; Quan Chen |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-7 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Chinese Academy of Sciences, China; |
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