title: Glutathione-s-transferases as determinants of cell survival and death.
abstract: CONCLUSIONS
  The family of glutathione S-transferases (GSTs) is part of a cellular Phase II detoxification program composed of multiple isozymes with functional human polymorphisms that have the capacity to influence individual response to drugs and environmental stresses. Catalytic activity is expressed through GST dimer-mediated thioether conjugate formation with resultant detoxification of a variety of small molecule electrophiles.
  
  
  BACKGROUND
  More recent work indicates that in addition to the classic catalytic functions, specific GST isozymes have other characteristics that impact cell survival pathways in ways unrelated to detoxification. These characteristics include the following: regulation of mitogen-activated protein kinases; facilitation of the addition of glutathione to cysteine residues in certain proteins (S-glutathionylation); as a novel cellular partner of the human papilloma virus-16 E7 oncoprotein playing a pivotal role in preventing cell death in infected human cells; mitogenic influence in myeloproliferative pathways; participant in the process of cocaine addiction.
  
  
  RESULTS
  Some of these functions have provided a platform for targeting GST with novel small molecule therapeutics, particularly in cancer where evidence of clinical applications is emerging.
  
  
  CONCLUSIONS
  Our evolving understanding of the GST superfamily and their divergent expression patterns in individuals make them attractive candidates for translational studies in a variety of human pathologies. In addition, their role in regulating cell fate in signaling and cell death pathways has opened up a significant functional complexity that extends well beyond standard detoxification reactions.
authors.affiliation: Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425-5050, USA. tewk@musc.edu
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Tew
authors.forename: Danyelle M
authors.initials: DM
authors.lastname: Townsend
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics / Q000502:physiology*; D002470:Cell Survival / Q000235:genetics / Q000502:physiology*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological
chemical_list: D005982:Glutathione Transferase