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

doi:10.1093/embo-reports/kve046

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 journal › Article › peer-review

1008 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 language	English
Pages (from-to)	222-228
Number of pages	7
Journal	EMBO Reports
Volume	2
Issue number	3
DOIs	https://doi.org/10.1093/embo-reports/kve046
Publication status	Published - 2001
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Genetics

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title = "ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis",

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.",

author = "Kei Tobiume and Atsushi Matsuzawa and Takumi Takahashi and Hideki Nishitoh and Morita, {Kei Ichi} and Kohsuke Takeda and Osamu Minowa and Kohei Miyazono and Tetsuo Noda and Hidenori Ichijo",

year = "2001",

doi = "10.1093/embo-reports/kve046",

language = "English",

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T1 - ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis

AU - Tobiume, Kei

AU - Matsuzawa, Atsushi

AU - Takahashi, Takumi

AU - Nishitoh, Hideki

AU - Morita, Kei Ichi

AU - Takeda, Kohsuke

AU - Minowa, Osamu

AU - Miyazono, Kohei

AU - Noda, Tetsuo

AU - Ichijo, Hidenori

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

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SN - 1469-221X

VL - 2

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EP - 228

JO - EMBO Reports

JF - EMBO Reports

IS - 3

ER -

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

Abstract

ASJC Scopus subject areas

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