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

Wu, Yifan; Fan, Yumei; Xue, Bin; Luo, Lan; Shen, Jiayin; Zhang, S; Jiang, Yong; Yin, Zhimin

doi:10.1038/sj.onc.1209576

Cited by 214 publications

(163 citation statements)

References 67 publications

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“…We suggest that GST pi predominantly utilizes a different interface for other protein-protein interactions that is distinguishable from the homodimeric interface. GST pi appears to form complexes with other proteins such as Jun N-terminal kinase [30][31][32] and tumor necrosis factor alpha [33]. If the other proteins interact entirely with the same site of GST pi occupied by 1-Cys Prx, complexes with these proteins seem likely to form with a GST monomer.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the complex of glutathione S-transferase pi and 1-cysteine peroxiredoxin

Ralat¹,

Misquitta²,

Manevich³

et al. 2008

Archives of Biochemistry and Biophysics

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Glutathione S-transferase pi has been shown to reactivate 1-cysteine peroxiredoxin (1-Cys Prx) by formation of a complex. A model of the complex was proposed based on the crystal structures of the two enzymes. We have now characterized the complex of GST pi/1-Cys Prx by determining the M w of the complex, by measuring the catalytic activity of the GST pi monomer, and by identifying the interaction sites between GST pi and 1-Cys Prx. The M w of the purified GST pi/1-Cys Prx complex is 50,200 at pH 8.0 in the presence of 2.5 mM glutathione, as measured by light scattering, providing direct evidence that the active complex is a heterodimer composed of equimolar amounts of the two proteins. In the presence of 4 M KBr, GST pi is dissociated to monomer and retains catalytic activity, but the K m value for GSH is increased substantially. To identify the peptides of GST pi that interact with 1-Cys Prx, GST pi was digested with V8 protease and the peptides were purified. The binding by 1-Cys Prx of each of four pure GST pi peptides (residues 41-85, 115-124, 131-163, and 164-197) was investigated by protein fluorescence titration. An apparent stoichiometry of 1 mol/subunit 1-Cys Prx was measured for each peptide and the formation of the heterodimer is decreased when these peptides are included in the incubation mixture. These results support our proposed model of the heterodimer. KeywordsGlutathione S-transferase pi; 1-Cys peroxiredoxin; Heterodimer Glutathione S-transferases (GSTs 1 ), which catalyze the nucleophilic attack by the thiol of glutathione on electrophilic substrates, constitute a family of enzymes important in the detoxification of xenobiotics, endogenous compounds, and the products of oxidative stress [1,2]. The pi isozyme (GST pi), crystallized as a homodimer with a subunit molecular * Corresponding author. Fax: +1 302 831 6335. rfcolman@chem.udel.edu (R.F. Colman). 1 Abbreviations used: GST, glutathione S-transferase; GST pi, pi-class glutathione S-transferase; 1-Cys Prx, 1-Cysteine peroxiredoxin; Ni-NTA, nickel-nitriloacetic acid agarose; TRIS, tris (hydroxymethyl) aminomethane; EDTA, disodium ethylenediamine tetraacetate; MES, 2-(N-morpholino) ethane-sulfonate; WT, wild-type; GSH, glutathione; CDNB, 1-chloro-2,4-dinitrobenzene; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript weight of 23,500, is of particular interest because it exhibits diverse roles in mammalian cells: it provides a defense against carcinogenesis, since it catalyzes the inactivation of known carcinogens [3]; it contributes significantly to the development of resistance to cancer chemotherapy, since GST pi levels increase in tumors and the enzyme metabolizes key anticancer drugs [4][5][6][7]; and it promotes the cellular response to oxidative stress, since GST pi has recently been reported to activate the anti-oxidant enzyme 1-Cys peroxiredoxin [8,9].1-Cys peroxiredoxin (1-Cys Prx, Prdx 6, Prx VI, and AOP2), a homodime...

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Section: Discussionmentioning

confidence: 99%

Characterization of the complex of glutathione S-transferase pi and 1-cysteine peroxiredoxin

Ralat¹,

Misquitta²,

Manevich³

et al. 2008

Archives of Biochemistry and Biophysics

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“…The NBD derivatives 1e40 were obtained by nucleophilic displacement reactions between the commercially available 4-chloro-7-nitrobenzo[c] [1,2,5] The not commercially available thiols were obtained by the reactions reported in Schemes 2e6. The thiophenols 41 and 43e50 were obtained by simultaneous acid activation/thiol protection of the commercial 4-mercaptobenzoic or 3-(4-mercaptophenyl)propionic acids with ethyl chloroformate in dimethoxyethane in the presence of N-methylmorpholine at room temperature, followed first by coupling with an appropriate amine and then by thiol deprotection with sodium methoxide in dry MeOH at room temperature.…”

Section: Chemistrymentioning

confidence: 99%

Synthesis and structure–activity relationship of new cytotoxic agents targeting human glutathione-S-transferases

Rotili

Luca

Tarantino

et al. 2015

European Journal of Medicinal Chemistry

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“…In fact, Adler et al 2 had demonstrated that GSTP1-1 efficiently inhibits the activity of JNK by forming a GSTP1-1 : JNK heterocomplex. Furthermore, Wu et al 3 have recently shown that GSTP1-1 inhibits TRAF2 in human cervical carcinoma HeLa cells. TRAF2 is an adaptor protein which mediates the signal transduction of different receptors 4 and it is required for the activation of the apoptosis signal-regulating kinase (ASK1), which in turn activates both mitogen-activated protein kinase (MKK)4/7-JNK and MKK3/4/6-p38 signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Targeting GSTP1-1 induces JNK activation and leads to apoptosis in cisplatin-sensitive and -resistant human osteosarcoma cell lines

Filomeni

Pezzola

et al. 2012

Mol. BioSyst.

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The effect of the glutathione transferase P1-1 (GSTP1-1) targeting has been investigated in both sensitive (U-2OS) and cisplatin-resistant (U-2OS/CDDP4 mg) human osteosarcoma cell lines. Despite the different enzyme's content, inhibition of GSTP1-1 by 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) causes the activation of c-Jun N-terminal kinase (JNK) and apoptosis in both cell lines. However, different time courses of JNK activation and cell responses are observed. Whereas in the U-2OS/CDDP4 mg cell line drug treatment results in an early increase of caspase activity and secondary necrosis, in the U-2OS cells it mainly causes an early cell cycle arrest followed by apoptosis. In order to elucidate the action mechanism of NBDHEX we performed a proteomic investigation by label-free nLC-MS E . The high-throughput analysis associated with a bioinformatic tool suggested the involvement of the TNF receptor associated factor (TRAF) family in the cellular response to the drug treatment. We report experimental evidence of the interaction between GSTP1-1 and TRAF2 and we demonstrate that NBDHEX is able to dissociate the GSTP1-1 : TRAF2 complex. This restores the TRAF2 : ASK1 signaling, thereby leading to the simultaneous and prolonged activation of JNK and p38. These mitogenactivated protein kinases (MAPKs) mediate different effects: JNK is crucial for apoptosis, whereas p38 causes an increase in the p21 level and a concomitant cell cycle arrest. Our study shows that GSTP1-1 plays an important regulatory role in TRAF signaling of osteosarcoma and discloses new features of the action mechanism of NBDHEX that suggest potentially practical consequences of these findings.

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

Cited by 214 publications

References 67 publications

Characterization of the complex of glutathione S-transferase pi and 1-cysteine peroxiredoxin

Characterization of the complex of glutathione S-transferase pi and 1-cysteine peroxiredoxin

Synthesis and structure–activity relationship of new cytotoxic agents targeting human glutathione-S-transferases

Targeting GSTP1-1 induces JNK activation and leads to apoptosis in cisplatin-sensitive and -resistant human osteosarcoma cell lines

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