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Originally published In Press as doi:10.1074/jbc.M004167200 on July 31, 2000

J. Biol. Chem., Vol. 275, Issue 42, 32611-32616, October 20, 2000
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Cadmium-inducible Expression of the Yeast GSH1 Gene Requires a Functional Sulfur-Amino Acid Regulatory Network*

Ulla H. DormerDagger §, John WestwaterDagger §, Niall F. McLarenDagger , Nicholas A. Kent||, Jane Mellor||, and Derek J. JamiesonDagger **

From the Dagger  Department of Biological Sciences, Heriot-Watt University, Riccarton, Edinburgh EH14 4AS, Scotland and the || Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom

Glutathione (gamma -L-glutamyl-L-cysteinylglycine) is an important antioxidant molecule, helping to buffer the cell against free radicals and toxic electrophiles. Expression of the yeast GSH1 gene, encoding the first enzyme involved in glutathione biosynthesis, gamma -glutamylcysteine synthetase, is regulated by oxidants and the heavy metal cadmium at the level of transcription. We present evidence that the transcription factors involved in controlling the network of sulfur amino acid metabolism genes are also responsible for regulating GSH1 expression in response to cadmium. In particular the transcription factors Met-4, Met-31, and Met-32 are essential for cadmium-mediated regulation of gene expression, whereas the DNA-binding protein Cbf1 appears to play a negative role in controlling GSH1 expression.

* This work was supported in part by Grant 97/G08324 from the Biotechnology and Biological Science Research Council and the Society for General Microbiology.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.

§ These authors contributed equally to the work.

Supported by a Biotechnology and Biological Science Research Council postgraduate studentship.

** To whom correspondence should be addressed. Tel.: 44-131-451-3644; Fax: 44-131-451-3009; E-mail: d.j.jamieson@hw.ac.uk.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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