Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway

Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway
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DOI:
10.1126/science.288.5467.870
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发表时间:
2000-05-05
期刊:
影响因子:
56.9
通讯作者:
Davis, RJ
Davis, RJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Tournier, C;Hess, P;Davis, RJ

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当细胞暴露在紫外线(UV)辐射下时,c-jun氨基末端激酶(JNK)被激活。然而,JNK激活在紫外线照射的细胞中的功能结果还没有确定。这表明JNK是紫外线诱导原代小鼠胚胎成纤维细胞凋亡所必需的。同时靶向干扰所有功能JNK基因的成纤维细胞可抵抗紫外线刺激的细胞凋亡。JNK的缺失导致了线粒体死亡信号通路的缺陷,包括不能释放细胞色素c。这些数据表明,线粒体受到JNK通路促凋亡信号转导的影响。
The c-Jun NH2-terminal kinase (JNK) is activated when cells are exposed to ultraviolet (UV) radiation. However, the functional consequence of JNK activation in UV-irradiated cells has not been established. It is shown here that JNK is required for UV-induced apoptosis in primary murine embryonic fibroblasts. Fibroblasts with simultaneous targeted disruptions of all the functional Jnk genes were protected against UV-stimulated apoptosis. The absence of JNK caused a defect in the mitochondrial death signaling pathway, including the failure to release cytochrome c. These data indicate that mitochondria are influenced by proapoptotic signal transduction through the JNK pathway.