JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis
JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis
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DOI：
10.1073/pnas.0438011100
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发表时间：
2003-03-04
影响因子：
11.1
通讯作者：
Davis, RJ
中科院分区：
文献类型：
--
作者：
Lei, K;Davis, RJ
c-Jun nh2末端激酶（JNK）在细胞暴露于环境胁迫（包括紫外线辐射）时被激活。基因破坏研究表明，JNK在通过Bax/ bak依赖机制的线粒体途径介导的紫外线刺激的细胞凋亡中是必不可少的。在这里，我们证明JNK磷酸化了bcl2相关蛋白的bh3亚群中的两个成员（Bim和Bmf），这两个成员通常通过与动力蛋白和肌凝蛋白V运动复合物结合而被隔离。JNK的磷酸化引起运动复合物的释放。因此，这些促凋亡的BH3-only蛋白在JNK信号转导途径和Bax/ bak依赖性线粒体凋亡机制之间提供了分子联系。
The c-Jun NH2-terminal kinase (JNK) is activated when cells are exposed to environmental stress, including UV radiation. Gene disruption studies demonstrate that JNK is essential for UV-stimulated apoptosis mediated by the mitochondrial pathway by a Bax/Bak-dependent mechanism. Here, we demonstrate that JNK phosphorylates two members of the BH3-only subgroup of Bcl2-related proteins (Bim and Bmf) that are normally sequestered by binding to dynein and myosin V motor complexes. Phosphorylation by JNK causes release from the motor complexes. These proapoptotic BH3-only proteins therefore provide a molecular link between the JNK signal transduction pathway and the Bax/Bak-dependent mitochondrial apoptotic machinery.