| Natural Diterpenoid Compound Elevates Expression of Bim Protein, Which Interacts with Antiapoptotic Protein Bcl-2, Converting It to Proapoptotic Bax-like Molecule | |
Zhao, Lixia2,3; He, Feng4; Liu, Haiyang1 ; Zhu, Yushan2,3; Tian, Weili2,3; Gao, Ping2,3; He, Hongping1; Yue, Wen2,3; Lei, Xiaobo2,3; Ni, Biyun2,3; Wang, Xiaohui2,3; Jin, Haijing2,3; Hao, Xiaojiang1; Lin, Jialing4; Chen, Quan2,3
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| 2012-01-06 | |
| 发表期刊 | JOURNAL OF BIOLOGICAL CHEMISTRY
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| 卷号 | 287期号:2页码:1054-1065 |
| 摘要 | 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 knock-out 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; this was accompanied by oligomerization of these proteins and deep embedding of 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 independently of Bax and Bak. Because Bcl-2 family proteins play important roles in cancer development and relapse, this novel cell death mechanism can be explored for developing more effective anticancer therapeutics. |
| DOI | 10.1074/jbc.M111.264481 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000299170300022 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.kib.ac.cn/handle/151853/20452 |
| 专题 | 植物化学与西部植物资源持续利用国家重点实验室 |
| 作者单位 | 1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources W China, Kunming 650204, Peoples R China 2.Chinese Acad Sci, State Key Lab Biomembrane & Membrane Biotechnol, Inst Zool, Joint Lab Apoptosis & Mitochondrial Biol, Beijing 100101, Peoples R China 3.Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China 4.Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73126 USA |
| 推荐引用方式 GB/T 7714 | Zhao, Lixia,He, Feng,Liu, Haiyang,et al. Natural Diterpenoid Compound Elevates Expression of Bim Protein, Which Interacts with Antiapoptotic Protein Bcl-2, Converting It to Proapoptotic Bax-like Molecule[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2012,287(2):1054-1065. |
| APA | Zhao, Lixia.,He, Feng.,Liu, Haiyang.,Zhu, Yushan.,Tian, Weili.,...&Chen, Quan.(2012).Natural Diterpenoid Compound Elevates Expression of Bim Protein, Which Interacts with Antiapoptotic Protein Bcl-2, Converting It to Proapoptotic Bax-like Molecule.JOURNAL OF BIOLOGICAL CHEMISTRY,287(2),1054-1065. |
| MLA | Zhao, Lixia,et al."Natural Diterpenoid Compound Elevates Expression of Bim Protein, Which Interacts with Antiapoptotic Protein Bcl-2, Converting It to Proapoptotic Bax-like Molecule".JOURNAL OF BIOLOGICAL CHEMISTRY 287.2(2012):1054-1065. |
| 条目包含的文件 | ||||||
| 文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 | ||
| 1054.full.pdf（2908KB） | 开放获取 | CC BY-NC-ND | 浏览 下载 | |||
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