Ure2, a prion precursor with homology to glutathione S-transferase, protects Saccharomyces cerevisiae cells from heavy metal ion and oxidant toxicity.
Ure2, the protein that negatively regulates GATA factor (Gln3, Gat1)-mediated transcription in Saccharomyces cerevisiae, possesses prion-like characteristics. Identification of metabolic and environmental factors that influence prion formation as well as any activities that prions or prion precursors may possess are important to understanding them and developing treatment strategies for the diseases in which they participate. Ure2 exhibits primary sequence and three-dimensional homologies to known glutathione S-transferases. However, multiple attempts over nearly 2 decades to demonstrate Ure2-mediated S-transferase activity have been unsuccessful, leading to the possibility that Ure2 may well not participate in glutathionation reactions. Here we show that Ure2 is required for detoxification of glutathione S-transferase substrates and cellular oxidants. ure2 Delta mutants are hypersensitive to cadmium and nickel ions and hydrogen peroxide. They are only slightly hypersensitive to diamide, which is nitrogen source-dependent, and minimally if at all hypersensitive to 1-chloro-2,4-dinitrobenzene, the most commonly used substrate for glutathione S-transferase enzyme assays. Therefore, Ure2 shares not only structural homology with various glutathione S-transferases, but ure2 mutations possess the same phenotypes as mutations in known S. cerevisiae and Schizosaccharomyces pombe glutathione S-transferase genes. These findings are consistent with Ure2 serving as a glutathione S-transferase in S. cerevisiae.
Rai
Rajendra
R
Department of Molecular Sciences, University of Tennessee, Memphis, Tennessee 38163, USA.
Tate
Jennifer J
JJ
Cooper
Terrance G
TG
D000641:Ammonia / Q000494:pharmacology; D003470:Culture Media; D005816:Genetic Complementation Test; D018698:Glutamic Acid / Q000494:pharmacology; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase / Q000737:chemistry*; D007700:Kinetics; D019216:Metals, Heavy / Q000633:toxicity*; D016877:Oxidants / Q000633:toxicity*; D010957:Plasmids; D011328:Prions / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D003470:Culture Media; D019216:Metals, Heavy; D016877:Oxidants; D011328:Prions; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D018698:Glutamic Acid; D000641:Ammonia; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae; D005982:Glutathione Transferase