Cadmium-inducible expression of the yeast GSH1 gene requires a functional sulfur-amino acid regulatory network

Glutathione (?-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, ?-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.