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J. Biol. Chem., Vol. 278, Issue 15, 12826-12833, April 11, 2003
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From the Department of Molecular Sciences, University of Tennessee,
Memphis, Tennessee 38163
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
Ure2, a Prion Precursor with Homology to Glutathione
S-Transferase, Protects Saccharomyces
cerevisiae Cells from Heavy Metal Ion and Oxidant
Toxicity*
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.
*
This work was supported by National Institutes of Health
Grant GM-35642.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.: 901-448-6179;
Fax: 901-448-8462; E-mail: tcooper@utmem.edu.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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