DOSAGE-DEPENDENT MODULATION OF GLUCOSE REPRESSION BY MSN3 (STD1) IN SACCHAROMYCES-CEREVISIAE

The SNF1 protein kinase of Saccharomyces cerevisiae is required to rel ieve glucose repression of transcription. To identify components of th e SNF1 pathway, we isolated multicopy suppressors of defects caused by loss of SNF4, an activator of the SNF1 kinase. Increased dosage of th e MSN3 gene restored invertase expression in snf4 mutants and also rel ieved glucose repression in the wild type. Deletion of MSN3 caused no substantial phenotype, and we identified a homolog, MTH1, encoding a p rotein 61% identical to MSN3, Both are also homologous to chicken fimb rin, human plastin, and yeast SAC6 ever a 43-residue region. Deletion of MSN3 and MTH1 together impaired derepression of invertase in respon se to glucose limitation. Finally, MSN3 physically interacts with the SNF1 protein kinase, as assayed by a two-hybrid system and by in vitro binding studies. MSN3 is the same gene as STD1, a multicopy suppresso r of defects caused by overexpression of the C terminus of TATA-bindin g protein (R. W. Ganster, W. Shen, and N. C. Schmidt, Mel. Cell. Biol. 13:3650-3659, 1993). Taken together, these data suggest that MSN3 mod ulates the regulatory response to glucose and may couple the SNF1 path way to transcription.