Ure2, a prion precursor with homology to glutathione S-transferase, protects Saccharomyces cerevisiae cells from heavy metal ion and oxidant toxicity

Rajendra Rai, Jennifer J. Tate, Terrance Cooper

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

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. ure2A 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.

Original languageEnglish (US)
Pages (from-to)12826-12833
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number15
DOIs
StatePublished - Apr 11 2003

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Heavy Ions
Prions
Heavy Metals
Glutathione Transferase
Heavy ions
Oxidants
Yeast
Metal ions
Toxicity
Saccharomyces cerevisiae
Schizosaccharomyces
GATA Transcription Factors
Diamide
Dinitrochlorobenzene
Detoxification
Mutation
Enzyme Assays
Substrates
Transcription
Transferases

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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Ure2, a prion precursor with homology to glutathione S-transferase, protects Saccharomyces cerevisiae cells from heavy metal ion and oxidant toxicity. / Rai, Rajendra; Tate, Jennifer J.; Cooper, Terrance.

In: Journal of Biological Chemistry, Vol. 278, No. 15, 11.04.2003, p. 12826-12833.

Research output: Contribution to journalArticle

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