JNK promotes Bax translocation to mitochondria through phosphorylation of 14-3-3 proteins
JNK promotes Bax translocation to mitochondria through phosphorylation of 14-3-3 proteins
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DOI：
10.1038/sj.emboj.7600194
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发表时间：
2004-04-21
期刊：
影响因子：
11.4
通讯作者：
Gotoh, Y
中科院分区：
文献类型：
--
作者：
Tsuruta, F;Sunayama, J;Gotoh, Y
靶向基因破坏研究已证实，c-Jun NH2 末端激酶 (JNK) 是应激诱导的线粒体细胞色素 c 释放和细胞凋亡所必需的，而 Bcl-2 相关蛋白的 Bax 亚家族对于 JNK 依赖性细胞凋亡至关重要。然而，JNK 调节 Bax 的机制仍未解决。在这里，我们证明激活的 JNK 通过 Bax 细胞质锚定蛋白 14-3-3 的磷酸化促进 Bax 易位至线粒体。 14-3-3 的磷酸化导致 Bax 从该蛋白质上解离。 14-3-3 磷酸化缺陷突变体的表达可阻断 JNK 诱导的 Bax 易位至线粒体、细胞色素 c 释放和细胞凋亡。总的来说，这些结果揭示了 Bax 调节应激诱导细胞凋亡的关键机制。
Targeted gene disruption studies have established that the c-Jun NH2-terminal kinase (JNK) is required for the stress-induced release of mitochondrial cytochrome c and apoptosis, and that the Bax subfamily of Bcl-2-related proteins is essential for JNK-dependent apoptosis. However, the mechanism by which JNK regulates Bax has remained unsolved. Here we demonstrate that activated JNK promotes Bax translocation to mitochondria through phosphorylation of 14-3-3, a cytoplasmic anchor of Bax. Phosphorylation of 14-3-3 led to dissociation of Bax from this protein. Expression of phosphorylation-defective mutants of 14-3-3 blocked JNK-induced Bax translocation to mitochondria, cytochrome c release and apoptosis. Collectively, these results have revealed a key mechanism of Bax regulation in stress-induced apoptosis.