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The role of glutathione S-transferase P in signaling pathways and S-glutathionylation in cancer
Authors:Tew Kenneth D  Manevich Yefim  Grek Christina  Xiong Ying  Uys Joachim  Townsend Danyelle M
Institution:
  • a Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA
  • b Department of Pharmaceutical and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USA
  • Abstract:Glutathione S-transferase P is abundantly expressed in some mammalian tissues, particularly those associated with malignancies. While the enzyme can catalyze thioether bond formation between some electrophilic chemicals and GSH, novel nondetoxification functions are now ascribed to it. This review summarizes recent material that implicates GSTP in mediating S-glutathionylation of specific clusters of target proteins and in reactions that define a negative regulatory role in some kinase pathways through ligand or protein:protein interactions. It is becoming apparent that GSTP participates in the maintenance of cellular redox homeostasis through a number of convergent and divergent mechanisms. Moreover, drug platforms that have GSTP as a target have produced some interesting preclinical and clinical candidates.
    Keywords:Glutathione  Glutathione S-transferase  c-jun NH2 kinase  S-glutathionylation  Signaling pathways  Post-translational modification  Bone marrow  Myeloproliferation  Cancer drug development  Cancer  Genetic polymorphisms
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