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

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.

Pubmed ID: 11266364


  • Tobiume K
  • Matsuzawa A
  • Takahashi T
  • Nishitoh H
  • Morita K
  • Takeda K
  • Minowa O
  • Miyazono K
  • Noda T
  • Ichijo H


EMBO reports

Publication Data

March 29, 2001

Associated Grants


Mesh Terms

  • Animals
  • Antigens, CD95
  • Apoptosis
  • Cells, Cultured
  • Enzyme Activation
  • Hydrogen Peroxide
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinase 5
  • MAP Kinase Kinase Kinases
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases
  • Signal Transduction
  • Tumor Necrosis Factor-alpha
  • p38 Mitogen-Activated Protein Kinases