2. Academic Validation
  3. ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis

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

  • EMBO Rep. 2001 Mar;2(3):222-8. doi: 10.1093/embo-reports/kve046.
K Tobiume 1,  A Matsuzawa,  T Takahashi,  H Nishitoh,  K Morita,  K Takeda,  O Minowa,  K Miyazono,  T Noda,  H Ichijo
Affiliations

Affiliation

  • 1 Laboratory of Cell Signaling, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
PMID: 11266364 DOI: 10.1093/embo-reports/kve046
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.

Figures