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

K Tobiume, A Matsuzawa, T Takahashi, H Nishitoh… - EMBO …, 2001 - embopress.org
K Tobiume, A Matsuzawa, T Takahashi, H Nishitoh, K Morita, K Takeda, O Minowa
EMBO reports, 2001embopress.org
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 …
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.
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