NR ANOC
AU Rai,R.; Tate,J.J.; Cooper,T.G.
TI Ure2, a prion precursor with homology to glutathione S-transferase, protects Saccharomyces cerevisiae cells from heavy metal ion and oxidant toxicity
QU The Journal of Biological Chemistry 2003 Jan 31
PT journal article
AB Ure2, the protein that negatively regulates GATA-factor (Gln3, Dal80) -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 under-standing 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 two decades to demon-strate 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. ure2D 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 CDNB, 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 pombe glutathione S-transferase genes. These findings are consistent with Ure2 serving as a glutathione S-transferase in S. cerevisiae.
AD Microbiology and Immunology, University of Tennessee, Memphis, TN 38163.
SP englisch