ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis
ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis
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DOI：
10.1093/embo-reports/kve046
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发表时间：
2001-03-01
期刊：
影响因子：
7.7
通讯作者：
Ichijo, H
中科院分区：
文献类型：
--
作者：
Tobiume, K;Matsuzawa, A;Ichijo, H
凋亡信号调节激酶（ASK）1响应于各种细胞毒性应激而被激活，包括TNF、Fas和活性氧（ROS）如H2 O2，并激活c-Jun NH 2-末端激酶（JNK）和p38。然而，JNK和p38信号通路在细胞凋亡中的作用一直存在争议。在这里，我们表明，通过删除小鼠中的ASK 1，TNF-和H2 O2诱导的持续激活的INK和p38在ASK 1（-/-）胚胎成纤维细胞中丢失，并且ASK 1（-/-）细胞对TNF-和H2 O2诱导的凋亡具有抗性。TNF而非Fas诱导的细胞凋亡需要ROS依赖性激活ASK 1-JNK/p38通路。因此，ASK 1是选择性地需要TNF-和氧化应激诱导的持续激活JNK/p38和凋亡。
Apoptosis signal-regulating kinase (ASK) 1 is activated in response to various cytotoxic stresses including TNF, Fas and reactive oxygen species (ROS) such as H2O2 and activates c-Jun NH2-terminal kinase (JNK) and p38. However, the roles of JNK and p38 signaling pathways during apoptosis have been controversial. Here we show that by deleting ASK1 in mice, TNF- and H2O2-induced sustained activations of INK and p38 are lost in ASK1(-/-) embryonic fibroblasts, and that ASK1(-/-) cells are resistant to TNF- and H2O2-induced apoptosis. TNF- but not Fas-induced apoptosis requires ROS-dependent activation of ASK1-JNK/p38 pathways. Thus, ASK1 is selectively required for TNF- and oxidative stress-induced sustained activations of JNK/p38 and apoptosis.