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

Kei Tobiume, Atsushi Matsuzawa, Takumi Takahashi, Hideki Nishitoh, Kei Ichi Morita, Kohsuke Takeda, Osamu Minowa, Kohei Miyazono, Tetsuo Noda, Hidenori Ichijo

Research output: Contribution to journalArticlepeer-review

908 Citations (Scopus)

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 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 JNK 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.

Original languageEnglish
Pages (from-to)222-228
Number of pages7
JournalEMBO Reports
Volume2
Issue number3
DOIs
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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