ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis
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Open Access
- 1 March 2001
- journal article
- research article
- Published by Springer Nature in EMBO Reports
- Vol. 2 (3) , 222-228
- https://doi.org/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 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.Keywords
This publication has 32 references indexed in Scilit:
- Requirement of JNK for Stress- Induced Activation of the Cytochrome c-Mediated Death PathwayScience, 2000
- From receptors to stress-activated MAP kinasesOncogene, 1999
- Deciphering the mammalian stress response – a stressful taskOncogene, 1999
- TUMOR NECROSIS FACTOR RECEPTOR AND Fas SIGNALING MECHANISMSAnnual Review of Immunology, 1999
- Early Activation of c-Jun N-terminal Kinase and p38 Kinase Regulate Cell Survival in Response to Tumor Necrosis Factor αJournal of Biological Chemistry, 1998
- Induction of Apoptosis by ASK1, a Mammalian MAPKKK That Activates SAPK/JNK and p38 Signaling PathwaysScience, 1997
- Stress-signalling kinase Sek1 protects thymocytes from apoptosis mediated by CD95 and CD3Nature, 1997
- Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosisNature, 1996
- Opposing Effects of ERK and JNK-p38 MAP Kinases on ApoptosisScience, 1995
- Apoptosis in the Pathogenesis and Treatment of DiseaseScience, 1995