Glutathione S-transferase-π is secreted as a monomer into human plasma by platelets and tumor cells

Kura, Toshiro; Takahashi, Yasuo; Takayama, Tetsuji; Ban, Noriyoshi; Saito, Tami; Kuga, Takashi; Niitsu, Yoshiro

doi:10.1016/0167-4838(95)00216-2

Cited by 30 publications

(26 citation statements)

References 19 publications

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“…1E) support this notion and indicate unequivocally the strong direct relationship between GSTP1 expression and suppression of JNK signaling. The results of the studies using the cell-penetrating TAT-Tyr-198 peptide, in which residues 194 -201 of the human GSTP1 were conjugated to the cell-permeable TAT sequence (47,48) to enhance intracellular delivery, showed this peptide to enhance EGF-induced JNK activation in GSTP1-overexpressing cells, whereas TAT-Y198F mutant and control TAT peptides had no effect on the JNK activity. This suggests a competition of the wild-type and Y198F mutant GSTP1 C terminus for binding to JNK.…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation of Glutathione S-Transferase P1 (GSTP1) by Epidermal Growth Factor Receptor (EGFR) Promotes Formation of the GSTP1-c-Jun N-terminal kinase (JNK) Complex and Suppresses JNK Downstream Signaling and Apoptosis in Brain Tumor Cells

Okamura¹,

Antoun²,

Keir³

et al. 2015

Journal of Biological Chemistry

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Background: GSTP1 is a downstream EGFR phosphorylation target. Results: EGFR-dependent C-terminal Tyr-198 phosphorylation shifts GSTP1 to the monomeric state, facilitates JNK binding and inhibition, and suppresses apoptosis in brain tumor cells. Conclusion: Enhanced suppression of JNK signaling by EGFR-phosphorylated GSTP1 provides a survival advantage for tumors. Significance: The GSTP1-EGFR cross-talk is a mechanism of tumor cell survival and drug resistance.

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Section: Discussionmentioning

confidence: 99%

Phosphorylation of Glutathione S-Transferase P1 (GSTP1) by Epidermal Growth Factor Receptor (EGFR) Promotes Formation of the GSTP1-c-Jun N-terminal kinase (JNK) Complex and Suppresses JNK Downstream Signaling and Apoptosis in Brain Tumor Cells

Okamura¹,

Antoun²,

Keir³

et al. 2015

Journal of Biological Chemistry

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“…With regard to the mechanism of GSTP1-1 being released from cells, it may not be simple leakage because GSTP1-1 in the medium exists in monomer form unlike the intracellular form, which is a homodimer (43).…”

Section: Figmentioning

confidence: 99%

Plasma Glutathione S -Transferase P1-1 as a Prognostic Factor in Patients with Advanced Non-Hodgkin’s Lymphoma (Stages III and IV)

Katahira

Takayama²,

Miyanishi³

et al. 2004

Clinical Cancer Research

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Purpose: This study aims to investigate whether the plasma level of glutathione S-transferase P1-1 (GSTP1-1), which is a phase II detoxifying enzyme known to be a resistance factor for anticancer drugs, could be a prognostic factor of de novo non-Hodgkin lymphoma (NHL) in clinical stages (CSs) III and IV.Experimental Design: Study population consisted of 80 NHL patients with no prior treatment: 12 patients were at CS I, 14 at CS II, 25 at CS III, and 29 at CS IV. All 54 patients at CS III or CS IV were treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). Plasma GSTP1-1 concentration was measured by ELISA. We stained lymph node tissues for GSTP1-1 using anti-GSTP1-1 monoclonal antibody 5F and quantitatively assessed the intensity of immunostaining by using the KS-400 image analyzing system.Results: There was a significant stepwise increment of plasma GSTP1-1 concentration from CS I to CS IV (P < 0.05). Of the 54 patients with CS III or IV treated with CHOP, 28 (52%) had elevated plasma GSTP1-1 levels. Plasma GSTP1-1 concentration tended to correlate with the intensity of GSTP1-1 expression in lymphoma tissues as assessed by immunostaining (P ‫؍‬ 0.07). The CR rates in patients at CS III and CS IV treated by CHOP, 55.2% (14 of 26) and 16.0% (5 of 28) for the low and high plasma GSTP1-1 groups, respectively, were significantly different (P < 0.01). For these two groups, the median survival times were 64 and 25 months, respectively (P < 0.01), and the median times to progression were 58 and 12 months, respectively (P < 0.01). There was no significant correlation between plasma GSTP1-1 concentrations and other NHL prognostic indicators in these patients as determined by univariate and multivariate analyses.Conclusion: These results showed that plasma GSTP1-1 is a useful prognostic factor for CS III and IV advanced NHL. Thus, it may be a promising strategy to treat NHL concomitantly with anticancer drugs and GSTP1-1-specific inhibitors.

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“…Several reports have documented that GSTP1 is found in the culture media of human tumor cells and human platelets as well as in human plasma and bile (Howie et al, 1989;Kura et al, 1996;Ranganathan et al, 2005). In addition, GSTP1 has been found to associate with the external surface of cells (Hemachand et al, 2002).…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, GSTP1 can function nonenzymatically by binding nonsubstrate ligands and reactive compounds, leading to sequestration and intracellular transport (Howie et al, 1989;Hayes et al, 2005;Ralat and Colman, 2006). Monomers of GSTP1 are found in the media of cultured tumor cells and human platelets as well as in human plasma and bile (Howie et al, 1989;Kura et al, 1996;Ranganathan et al, 2005). The passage of GSTP1 across the cell membrane has been proposed as an excretory pathway for bound ligands, but the mechanism by which GSTP1 might traverse the membrane is not understood.…”

Section: Introductionmentioning

confidence: 99%

Glutathione Transferase P1 Interacts Strongly with the Inner Leaflet of the Plasma Membrane

Qazi

Pérez²,

Sam

et al. 2011

Drug Metab Dispos

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ABSTRACT:GSH transferases (GSTs) are a superfamily of proteins best known for detoxifying harmful electrophilic compounds by catalyzing their conjugation with GSH. GSTP1 is the most prevalent and widely distributed GST in human tissues, helping to detoxify a diverse array of carcinogens and drugs. In contrast with its protective role, overexpression of GSTP1 in a variety of malignancies is associated with a poor prognosis due to failure of chemotherapy. Although GSTP1 is classified as a cytosolic GST, we discovered previously that it is associated with the plasma membrane of the small cell lung cancer cell lines, H69 and H69AR. In the current study, endogenous and overexpressed GSTP1 in human embryonic kidney (HEK) 293 and MCF-7 cell lines, respectively, were found also to associate with the plasma membrane, indicating that this interaction is not unique to H69 and H69AR cells. GSTP1 immunostaining in HEK293 and MCF7-GSTP1 cells only occurred under permeabilized conditions, suggesting that GSTP1 is associated with the intracellular surface of the plasma membrane. Cell surface biotinylation studies confirmed this finding. Immunogold electron microscopy revealed the presence of GSTP1 in close proximity to the plasma membrane. GSTP1 was not dissociated from plasma membrane sheets by high salt [potassium iodide (KI; 1 M) or KI/EDTA (1 M/2 mM)] or alkaline Na 2 CO 3 (100 mM, pH 11.4), conditions known to strip peripherally associated membrane proteins. Thus, we report for the first time that GSTP1 is associated with the inner leaflet of the plasma membrane through a remarkably strong interaction.

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Glutathione S-transferase-π is secreted as a monomer into human plasma by platelets and tumor cells

Cited by 30 publications

References 19 publications

Phosphorylation of Glutathione S-Transferase P1 (GSTP1) by Epidermal Growth Factor Receptor (EGFR) Promotes Formation of the GSTP1-c-Jun N-terminal kinase (JNK) Complex and Suppresses JNK Downstream Signaling and Apoptosis in Brain Tumor Cells

Phosphorylation of Glutathione S-Transferase P1 (GSTP1) by Epidermal Growth Factor Receptor (EGFR) Promotes Formation of the GSTP1-c-Jun N-terminal kinase (JNK) Complex and Suppresses JNK Downstream Signaling and Apoptosis in Brain Tumor Cells

Plasma Glutathione S -Transferase P1-1 as a Prognostic Factor in Patients with Advanced Non-Hodgkin’s Lymphoma (Stages III and IV)

Glutathione Transferase P1 Interacts Strongly with the Inner Leaflet of the Plasma Membrane

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