Bcl-2家族蛋白调控线粒体膜通透性和细胞色素C释放的新机制
Functional conversion of Bcl-2 into a pro-apoptotic molecule to regulate mitochondrial cytochrome c release
查看参考文献19篇
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文摘
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Bcl-2家族蛋白在调控线粒体功能和细胞色素C释放中起重要作用。最近发现Bcl-2分子通过与其他促凋亡分子相互作用调控线粒体外膜通透性，其具体分子机制尚不完全清楚。本课题组采用化学生物学方法，在研究Bax/Bak非依赖的细胞凋亡途径中，发现了一些小分子化合物能够诱导Bim表达量急剧升高，Bim能转位到线粒体上，与Bcl-2相互作用增强，并直接促进Bcl-2构象变化。有意义的是，Bim可以诱导Bcl-2功能发生转换并能够形成大的复合体通道来介导细胞色素C释放。研究结果提示Bcl-2分子可变成促凋亡分子，参与Bax/Bak非依赖的细胞色素C释放和细胞凋亡。 |
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其他语种文摘
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Bcl-2 and its family proteins play pivotal roles in the regulation of the cytochrome c release and mitochondria functions. However, the mechanism on how Bcl-2 regulates mitochondrial outer membrane permeability is still not fully understood. We undertook a chemical biology approach to understand whether and how Bcl-2 regulates cytochrome c release in the absence of Bax and Bak. We identified several small compounds, such as gossypol, S-3 and PAO, that induced typical apoptosis in the bax/bak deficient cells. Mechanistic studies further revealed that these compounds are able to induce functional conversion of Bcl-2 into a Bax or Bak-like molecules. In particular, S-3 and PAO could induce the up-regulation of Bim which physically interacts with Bcl-2 at the MOM changing its conformation to form Bax-like pores which release cytochrome c and induce apoptosis. Since previous studies have generated overwhelming evidence showing that Bcl-2 is an anti-apoptotic molecule, it is surprising to find that Bim, a BH3-only protein and well known physiological inducer of apoptosis converts Bcl-2 to a Bax-like pro-apoptotic protein. |
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来源
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生命科学
,2011,23(11):1076-1080 【扩展库】
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关键词
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线粒体
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Bcl-2
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细胞凋亡
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细胞色素C
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地址
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1.
南开大学生命科学学院, 药物化学生物学国家重点实验室, 天津, 300071
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天津体育学院健康与运动系, 天津, 300381
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中国科学院动物研究所, 生物膜与膜生物工程国家重点实验室, 北京, 100101
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美国俄克拉荷马大学健康科学中心, 诺曼, 56581
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中国科学院昆明植物研究所, 昆明, 650204
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南开大学生命科学学院, 药物化学生物学国家重点实验室;;生物膜与膜生物工程国家重点实验室, 天津, 300071
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语种
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中文 |
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ISSN
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1004-0374 |
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学科
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细胞生物学 |
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基金
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国家自然科学基金
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文献收藏号
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CSCD:4389770
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