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ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis
Author(s) -
Tobiume Kei,
Matsuzawa Atsushi,
Takahashi Takumi,
Nishitoh Hideki,
Morita Keiichi,
Takeda Kohsuke,
Minowa Osamu,
Miyazono Kohei,
Noda Tetsuo,
Ichijo Hidenori
Publication year - 2001
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1093/embo-reports/kve046
Subject(s) - ask1 , p38 mitogen activated protein kinases , microbiology and biotechnology , apoptosis , kinase , reactive oxygen species , map kinase kinase kinase , signal transduction , tumor necrosis factor alpha , oxidative stress , biology , chemistry , protein kinase a , mitogen activated protein kinase kinase , immunology , biochemistry
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.