Regulation of JNK signaling by GSTp

Adler, Victor; Yin, Zhimin; Fuchs, Serge Y.; Benezra, Miriam; Rosario, Lilliam A.; Tew, Kenneth D.; Pincus, Matthew R.; Sardana, Mohinder K.; Henderson, Colin J.; Wolf, Charles; Davis, Roger J.; Ronai, Ze’ev

doi:10.1093/emboj/18.5.1321

Cited by 1,012 publications

(876 citation statements)

References 55 publications

(83 reference statements)

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“…GSTp was demonstrated to be directly associated with JNK [188] and its monomeric form was shown to inhibit JNK activation in a manner that was independent on MEKK1-MKK4, the physiological upstream activators of JNK. In response to an oxidant stress, GSTp oligomerizes, and dissociates from JNK1, promoting its activation [189] (Figure 2, box 4). Importantly, mouse embryo fibroblasts from GSTp-null mice exhibited a high basal level of JNK activity, [189] and GSTp-null mice showed a phenotype of increased myeloproliferation, in association with activation of JNK and the JAK/STAT pathway [190], corroborating the functional significance of GSTp in the regulation of JNK, and potential other pathways in vivo.…”

Section: Redox Control Through Functional Dimerization Of Redox Enzymmentioning

confidence: 99%

“…In response to an oxidant stress, GSTp oligomerizes, and dissociates from JNK1, promoting its activation [189] (Figure 2, box 4). Importantly, mouse embryo fibroblasts from GSTp-null mice exhibited a high basal level of JNK activity, [189] and GSTp-null mice showed a phenotype of increased myeloproliferation, in association with activation of JNK and the JAK/STAT pathway [190], corroborating the functional significance of GSTp in the regulation of JNK, and potential other pathways in vivo. GSTp also is an important regulator of peroxiredoxin 6 (1-cysPrx), via a mechanism that involves heterodimerization of the oxidized catalytic cysteine of 1-cysPrx with pi GST followed by its GSH-mediated reduction and enzyme activation [191].…”

Section: Redox Control Through Functional Dimerization Of Redox Enzymmentioning

confidence: 99%

See 1 more Smart Citation

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

Janssen–Heininger¹,

Mossman²,

Heintz³

et al. 2008

Free Radical Biology and Medicine

688

646

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Section: Redox Control Through Functional Dimerization Of Redox Enzymmentioning

confidence: 99%

Section: Redox Control Through Functional Dimerization Of Redox Enzymmentioning

confidence: 99%

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

Janssen–Heininger¹,

Mossman²,

Heintz³

et al. 2008

Free Radical Biology and Medicine

688

646

View full text Add to dashboard Cite

“…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). The bacterial transcription factor, OxyR (57) and the eukaryotic transcription factors AP-1 (58) and NF-κB (59) also contain critical cysteine residues that are targets of signaling.…”

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

160

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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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“…Recently, Adler and co-workers have reported that GSTP1 can act to alter intracellular signaling through an interaction with Jun N-terminal kinase (JNK). 41 Decreased GSTP1 expression might therefore alter intracellular signaling and this effect would provide a plausible biochemical mechanism to explain a role in prostate carcinogenesis. The description of the effect of TER 199, a highly specific GSTP1 inhibitor, in stimulating growth of granulocytes further suggests a potentially important regulatory role for the GSTP1 protein.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of GSTP1 and related genes and prostate cancer risk

Beer

Evans

Hough

et al. 2002

Prostate Cancer Prostatic Dis

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Glutathione S-transferase P1 (GSTP1) is markedly downregulated in prostate cancer and prostatic intraepithelial neoplasia compared to normal prostate tissue. Downregulation of GSTP1 may, therefore, be an early event in prostate carcinogenesis. An A?G polymorphism at nucleotide 313 results in an amino acid substitution (Ile105Val) in the substrate binding site of GSTP1 and reduces catalytic activity of GSTP1. In a study of 36 prostate cancer patients, Harries et al. reported that the Ile/Ile genotype is associated with a decreased risk of prostate cancer (odds ratio 0.4 (0.17 -0.82)). We sought to confirm this finding and to examine the impact of this polymorphism together with several related polymorphisms implicated as risk factors for carcinogen-associated malignancies. One hundred and seventeen patients with prostate adenocarcinoma and 183 population-based controls were recruited to this case -control study. Genotyping of the GSTP1 (Ile105Val), GSTM1 (null), GSTT1 (null) and CYP1A1 (Ile462Val) genes was performed using polymerase chain reaction (PCR) based techniques on DNA prepared from peripheral blood. A questionnaire was used to collect demographic information from each subject. Cases were significantly older (P < 0.0001) and had significantly greater family history of prostate cancer (P < 0.0001), confirming known risk factors for this disease. By w 2 analysis, none of the genotype distributions varied among cases and controls. Using a logistic regression model to control for known risk factors we were also unable to demonstrate a significant association with prostate cancer for any of the polymorphisms tested. This population fails to identify a relationship between the above polymorphisms and prostate adenocarcinoma.

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Regulation of JNK signaling by GSTp

Abstract: Studies of low basal Jun N-terminal kinase (JNK) activity in non-stressed cells led us to identify a JNK inhibitor that was purified and identified as glutathione S-transferase

Cited by 1,012 publications

References 55 publications

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

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

Polymorphisms of GSTP1 and related genes and prostate cancer risk

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