ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis

被引：1025

作者：

Tobiume, K

Matsuzawa, A

Takahashi, T

Nishitoh, H

Morita, K

Takeda, K

Minowa, O

Miyazono, K

Noda, T

Ichijo, H

机构：

[1] Tokyo Med & Dent Univ, Lab Cell Signaling, Grad Sch, Bunkyo Ku, Tokyo 1138549, Japan

[2] Japanese Fdn Canc Res, Inst Canc, Dept Biochem, Tokyo 1708455, Japan

[3] Japanese Fdn Canc Res, Inst Canc, Dept Cell Biol, Tokyo 1708455, Japan

来源：

EMBO REPORTS | 2001年 / 2卷 / 03期

关键词：

D O I：

10.1093/embo-reports/kve046

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

收藏

页码：222 / 228

页数：7

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