ArticleThe Journal of biological chemistry2015
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.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- Identification of Crocin I as a positive modulator of GSTP1 with potential relevance to prostate cancer.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- 6PPDQ Promotes Cutaneous Squamous Cell Carcinoma Growth with PI3K-Akt/MMP9 Activation: Evidence from Integrated Network Toxicology and Experimental Investigation.International journal of molecular sciences · 2026Article
- Tissue-specific variability in protein expression of cytochrome P450 and glutathione S-transferase isoenzymes in non-small cell lung carcinoma.Arhiv za higijenu rada i toksikologiju · 2026Article
- STAT3/POSTN/GSTP1/JNK Axis Orchestrates Ferroptosis in Nucleus Pulposus Cells: A Potential Therapeutic Target for Intervertebral Disc Degeneration.Neurospine · 2026Article
- Unveiling the Role of GlutathioneACS pharmacology & translational science · 2026Review
- Posttranslational modifications remodel proteome-wide ligandability.Nature chemical biology · 2026Article
- Beyond the Very Important Pharmacogenes (VIPs): Uncovering Shadow Pharmacogenes in the Human Drug Response Network.ACS omega · 2026Article
- Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Structural and systems characterization of phosphorylation on metabolic enzymes identifies sex-specific metabolic reprogramming in obesity.Molecular cell · 2025Article
- Parallel phosphoproteomics and metabolomics map the global metabolic tyrosine phosphoproteome.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- SPAG6 overexpression decreases the pro-apoptotic effect of daunorubicin in acute myeloid leukemia cells through the ROS/JNK MAPK axis in a GSTP1-dependent manner.Frontiers in pharmacology · 2024Article
- Novel coumarin-6-sulfonamide-chalcone hybrids as glutathione transferase P1-1 inhibitors.PloS one · 2024Article
- A GSTP1-mediated lactic acid signaling promotes tumorigenesis through the PPP oxidative branch.Cell death & disease · 2023Article
- NUMA1 modulates apoptosis of esophageal squamous cell carcinoma cells through regulating ASK1-JNK signaling pathway.Cellular and molecular life sciences : CMLS · 2023Article
- The good Samaritan glutathione-S-transferase P1: An evolving relationship in nitric oxide metabolism mediated by the direct interactions between multiple effector molecules.Redox biology · 2023Review
- Implications of glutathione-S transferase P1 in MAPK signaling as a CRAF chaperone: In memory of Dr. Irving Listowsky.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2022Review
- Biomarkers and Mechanisms of Oxidative Stress-Last 20 Years of Research with an Emphasis on Kidney Damage and Renal Transplantation.International journal of molecular sciences · 2021Review
- GSTP1 as a novel target in radiation induced lung injury.Journal of translational medicine · 2021Review
- GlutathioneThe Journal of pharmacology and experimental therapeutics · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Under normal physiologic conditions, the glutathione S-transferase P1 (GSTP1) protein exists intracellularly as a dimer in reversible equilibrium with its monomeric subunits. In the latter form, GSTP1 binds to the mitogen-activated protein kinase, JNK, and inhibits JNK downstream signaling. In tumor cells, which frequently are characterized by constitutively high GSTP1 expression, GSTP1 undergoes phosphorylation by epidermal growth factor receptor (EGFR) at tyrosine residues 3, 7, and 198. Here we report on the effect of this EGFR-dependent GSTP1 tyrosine phosphorylation on the interaction of GSTP1 with JNK, on the regulation of JNK downstream signaling by GSTP1, and on tumor cell survival. Using in vitro and in vivo growing human brain tumors, we show that tyrosine phosphorylation shifts the GSTP1 dimer-monomer equilibrium to the monomeric state and facilitates the formation of the GSTP1-JNK complex, in which JNK is functionally inhibited. Targeted mutagenesis and functional analysis demonstrated that the increased GSTP1 binding to JNK results from phosphorylation of the GSTP1 C-terminal Tyr-198 by EGFR and is associated with a >2.5-fold decrease in JNK downstream signaling and a significant suppression of both spontaneous and drug-induced apoptosis in the tumor cells. The findings define a novel mechanism of regulatory control of JNK signaling that is mediated by the EGFR/GSTP1 cross-talk and provides a survival advantage for tumors with activated EGFR and high GSTP1 expression. The results lay the foundation for a novel strategy of dual EGFR/GSTP1 for treating EGFR+ve, GSTP1 expressing GBMs.
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