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

Tobiume, Kei; Matsuzawa, Atsushi; Takahashi, Takumi; Nishitoh, Hideki; Morita, Kei; Takeda, Kohsuke; Minowa, Osamu; Miyazono, Kohei; Noda, Tetsuo; Ichijo, Hidenori

doi:10.1093/embo-reports/kve046

Cited by 1,111 publications

(997 citation statements)

References 31 publications

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“…As stress can activate ASK1, a protein kinase of the MAPK kinase family that in turn activates the P38 MAPK signaling cascade, we were interested to investigate whether this was the case in our cells (Tobiume et al ., 2001). Thus, by down‐regulating ASK1 mRNA and significantly reducing its protein levels, we were able to show that even in the presence of a glucose‐free medium, neuronal cells did not show changes in pP38 and most importantly, the intracellular levels of tau phosphorylated were also unmodified compared with controls.…”

Section: Discussionmentioning

confidence: 99%

Glucose deprivation increases tau phosphorylation via P38 mitogen‐activated protein kinase

Lauretti

Praticò

2015

Aging Cell

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SummaryAlterations of glucose metabolism have been observed in Alzheimer's disease (AD) brain. Previous studies showed that glucose deprivation increases amyloidogenesis via a BACE‐1‐dependent mechanism. However, no data are available on the effect that this condition may have on tau phosphorylation. In this study, we exposed neuronal cells to a glucose‐free medium and investigated the effect on tau phosphorylation. Compared with controls, cells incubated in the absence of glucose had a significant increase in tau phosphorylation at epitopes Ser202/Thr205 and Ser404, which was associated with a selective activation of the P38 mitogen‐activated protein kinase. Pharmacological inhibition of this kinase prevented the increase in tau phosphorylation, while fluorescence studies revealed its co‐localization with phosphorylated tau. The activation of P38 was secondary to the action of the apoptosis signal‐regulating kinase 1, as its down‐regulation prevented it. Finally, glucose deprivation induced cell apoptosis, which was associated with a significant increase in both caspase 3 and caspase 12 active forms. Taken together, our studies reveal a new mechanism whereby glucose deprivation can modulate AD pathogenesis by influencing tau phosphorylation and suggest that this pathway may be a new therapeutic target for AD.

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Section: Discussionmentioning

confidence: 99%

Glucose deprivation increases tau phosphorylation via P38 mitogen‐activated protein kinase

Lauretti

Praticò

2015

Aging Cell

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“…The role of TRAF2-ASK1 association in TNF-atriggered sustained activation of JNK and p38 has been well documented (Hoeflich et al, 1999;Liu et al, 2000;Tobiume et al, 2001). TNF-a-induced production of ROS triggers the dissociation of Trx from ASK1 and consequently liberalizes ASK1 for binding with TRAF2.…”

Section: Gstp1-1 Modulates Tnf-a Signaling Y Wu Et Almentioning

confidence: 99%

“…As TRAF2-ASK1 axis is essential for mediating TNF-a and oxidative stresses stimulated apoptotic cell death (Tobiume et al, 2001;Noguchi et al, 2005), we also determined the effect of GSTP1-1 on TNF-ainduced HeLa cell apoptosis by microscopy ( Figure 7c) and flow cytometry using propidium iodide (PI) staining (Figure 7d). Exposure of GSTP1-1-knockdown HeLa cells to TNF-a plus CHX markedly enhanced apoptotic cell death.…”

Section: Gstp1-1 Modulates Tnf-a Signaling Y Wu Et Almentioning

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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“…Among the signaling proteins (and their critical cysteines) that have been well characterized are the PTPs, PTP1B (cys 215 ) (26,27,(34)(35)(36), low molecular weight PTP (cys12,17) (37-39) and Srchomology 2 domain-containing PTP (SHP-2) (40), the small G protein, Ras (cys 118 ) (41)(42)(43)(44), the large G proteins, G i (cys 267 ) and G o (cys 326 ) (45) and the lipid phosphatase, phosphatase and tensin homolog deleted on chromosome 10 (PTEN). In addition, as mentioned above, in its reduced form Trx binds and inhibits ASK1 and possibly other signaling proteins as well (46)(47)(48)(49)(50)(51)(52)(53). When oxidized by formation of a disulfide between the two cysteines in its active site, Trx dissociates from ASK1, allowing it to become activated (46)(47)(48)(49)(50)(51)(52)(53) (Figure 1).…”

Section: A Signaling Proteins In Which Critical Cysteines Are Modifiedmentioning

confidence: 99%

“…In addition, as mentioned above, in its reduced form Trx binds and inhibits ASK1 and possibly other signaling proteins as well (46)(47)(48)(49)(50)(51)(52)(53). When oxidized by formation of a disulfide between the two cysteines in its active site, Trx dissociates from ASK1, allowing it to become activated (46)(47)(48)(49)(50)(51)(52)(53) (Figure 1). Also, GSTΠ inhibits c-Jun-N-terminal kinase (JNK) but dissociates and allows JNK activation when its critical active site cysteine is oxidized (54)(55)(56).…”

Section: A Signaling Proteins In Which Critical Cysteines Are Modifiedmentioning

confidence: 99%

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

Forman

Fukuto

Miller

et al. 2008

Archives of Biochemistry and Biophysics

217

165

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During the past several years, major advances have been made in understanding how reactive oxygen species (ROS) and nitrogen species (RNS) participate in signal transduction. Identification of the specific targets and the chemical reactions involved still remains to be resolved with many of the signaling pathways in which the involvement of reactive species has been determined. Our understanding is that ROS and RNS have second messenger roles. While cysteine residues in the thiolate (ionized) form found in several classes of signaling proteins can be specific targets for reaction with H 2 O 2 and RNS, better understanding of the chemistry, particularly kinetics, suggests that for many signaling events in which ROS and RNS participate, enzymatic catalysis is more likely to be involved than non-enzymatic reaction. Due to increased interest in how oxidation products, particularly lipid peroxidation products, also are involved with signaling, a review of signaling by 4-hydroxy-2-nonenal (HNE) is included. This article focuses on the chemistry of signaling by ROS, RNS, and HNE and will describe reactions with selected target proteins as representatives of the mechanisms rather attempt to comprehensively review the many signaling pathways in which the reactive species are involved. Keywords signaling; glutathione; thioredoxin; oxidants; reactive oxygen species; thiols; peroxide; nitric oxide; peroxynitrite; 4-hydroxynonenal; cysteine; hydrogen peroxide; protein tyrosine phosphatase; reactive nitrogen species; eNOS; iNOS; nNOS; soluble guanylate cyclase; cGMP; tyrosine nitration; fatty acid nitration; NO-heme; NO-metal complexes; nitrite; protein kinase C; ERK; JNK; p38MAPK; tyrosine kinase receptors; calcium OVERVIEW OF SIGNALING BY REACTIVE SPECIESUnderstanding of the roles of reactive oxygen species (ROS), reactive nitrogen species (RNS) and the lipid peroxidation product, 4-hydroxy-2-nonenal (HNE) in signaling has evolved rapidly during the last decade. This has been markedly helped by identification of the specific targets in signaling pathways. In previous reviews, we defined how ROS, H 2 O 2 in particular,

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

Cited by 1,111 publications

References 31 publications

Glucose deprivation increases tau phosphorylation via P38 mitogen‐activated protein kinase

Glucose deprivation increases tau phosphorylation via P38 mitogen‐activated protein kinase

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

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

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