ASK1 Is Essential for JNK/SAPK Activation by TRAF2

Nishitoh, Hideki; Saitoh, Masao; Mochida, Yoshiyuki; Takeda, Kohsuke; Nakano, Hiroyasu; Rothe, Mike; Miyazono, Kohei; Ichijo, Hidenori

doi:10.1016/s1097-2765(00)80283-x

Cited by 608 publications

(522 citation statements)

References 40 publications

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“…The kinase assay using GST-cJun (1-79) has been described. 20 The amount of JNK protein was determined by immunoblotting with anti-JNK polyclonal antibody.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…ASK1 is activated in response to H 2 O 2 , TNF and ER stress through distinct mechanisms. 19,20 Overexpression of wild-type or activated mutant of ASK1 induces apoptosis in various cells through mitochondria-dependent caspase activation. 19,21,22 Recently, we showed that ROS-induced sustained activation of JNK is lost in ASK1 À/À MEFs and that ASK1 À/À cells are less susceptible than ASK1 þ / þ cells to ROS.…”

Section: Introductionmentioning

confidence: 99%

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Amyloid β induces neuronal cell death through ROS-mediated ASK1 activation

et al. 2004

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Amyloid b (Ab) is a main component of senile plaques in Alzheimer's disease and induces neuronal cell death. Reactive oxygen species (ROS), nitric oxide and endoplasmic reticulum (ER) stress have been implicated in Ab-induced neurotoxicity. We have reported that apoptosis signalregulating kinase 1 (ASK1) is required for ROS-and ER stress-induced JNK activation and apoptosis. Here we show the involvement of ASK1 in Ab-induced neuronal cell death. Ab activated ASK1 mainly through production of ROS but not through ER stress in cultured neuronal cells. Importantly, ASK1 À/À neurons were defective in Ab-induced JNK activation and cell death. These results indicate that ROS-mediated ASK1 activation is a key mechanism for Ab-induced neurotoxicity, which plays a central role in Alzheimer's disease.

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“…The kinase assay using GST-cJun (1-79) has been described. 20 The amount of JNK protein was determined by immunoblotting with anti-JNK polyclonal antibody.…”

Section: Western Blot Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Amyloid β induces neuronal cell death through ROS-mediated ASK1 activation

et al. 2004

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“…Two TRAF family proteins, TRAF2 and TRAF6, have been demonstrated to bind to and thereby activate ASK1. Gene-knockout experiments showed that TRAF2 was essential for TNF-a-stimulated ASK1-JNK activation (Lee et al, 1997;Nishitoh et al, 1998;Noguchi et al, 2005), and TRAF6-ASK1 axis is selectively required for lipopolysaccharide (LPS)-induced activation of p38 . To explore the possibility that TRAF2 or TRAF6 was related with the inhibitory effect of GSTP1-1 on TNF-a triggered ASK1-JNK signaling cascade, endogenous TRAF2 and TRAF6 in HeLa cells were immunoprecipitated with respective antibodies.…”

Section: Gstp1-1 Physically Interacts With Traf2mentioning

confidence: 99%

Human glutathione S-transferase P1-1 interacts with TRAF2 and regulates TRAF2–ASK1 signals

et al. 2006

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Human glutathione S-transferase P1-1 (GSTP1-1) is an ubiquitously expressed protein that plays an important role in the detoxification and xenobiotics metabolism. It has been shown that GSTP1-1 interacts with c-Jun NH 2 -terminal kinase (JNK) and suppresses its activity. Here, we report a novel function of GSTP1-1 in regulating tumor necrosis factor-a (TNF-a)-triggered signaling. The present experiments showed that GSTP1-1 physically associated with tumor necrosis factor receptor-associated factor 2 (TRAF2) in vivo and in vitro. Overexpression of GSTP1-1 inhibited TRAF2-induced activation of both JNK and p38 but not of nuclear factor-jB (NF-jB). Glutathione S-transferase P1-1 also attenuated TRAF2-enhanced apoptosis signal-regulating kinase 1 (ASK1) autophosphorylation and inhibited TRAF2-ASK1-induced cell apoptosis by suppressing the interaction of TRAF2 and ASK1. Conversely, silencing of GSTP1-1 expression through RNA interference (RNAi) resulted in increase of TNF-a-dependent TRAF2-ASK1 association followed by hyper-activation of ASK1 and JNK. A mutant GSTP1-1 lacking TRAF domain-binding motif exhibited a significant decline of capacity to bind TRAF2 and block TRAF2-ASK1 signaling compared with the wild type of GSTP1-1. Moreover, the glutathione-conjugating activity of GSTP1-1 was not involved in the regulation of TRAF2 signaling. These findings indicate that GSTP1-1 plays an important regulatory role in TNF-a-induced signaling by forming ligand-binding interactions with TRAF2, which provides a new insight for analysing the protective effects of GSTP1-1 in tumor cells.

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“…TRADD is a proapoptotic intermediary adaptor between the receptor and FADD. RIP also binds TRADD and is thought to participate in activation of the Jnk pathway, which also involves TRAFs and possibly Ask1 (Ashkenazi and Nishitoh et al, 1998). TRAFs, in particular TRAF2, are implicated in activation of an antiapoptotic pathway that stimulates NFkB activation via IkB inactivation (Ashkenazi and .…”

Section: Regulatory Connections Between C-myc and Death Receptorsmentioning

confidence: 99%