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- Title
ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis.
- Authors
Tobiume, K; Matsuzawa, A; Takahashi, T; Nishitoh, H; Morita, K; Takeda, K; Minowa, O; Miyazono, K; Noda, T; Ichijo, H
- Abstract
Apoptosis signal-regulating kinase (ASK) 1 is activated in response to various cytotoxic stresses including TNF, Fas and reactive oxygen species (ROS) such as H(2)O(2), and activates c-Jun NH(2)-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 H(2)O(2)-induced sustained activations of JNK and p38 are lost in ASK1(-/-) embryonic fibroblasts, and that ASK1(-/-) cells are resistant to TNF- and H(2)O(2)-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.
- Publication
EMBO reports, 2001, Vol 2, Issue 3, p222
- ISSN
1469-221X
- Publication type
Journal Article
- DOI
10.1093/embo-reports/kve046