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Genetics, Vol 126, 549-562, Copyright © 1990
INVESTIGATIONS |
The Translational Activator GCN3 Functions Downstream from GCN1 and GCN2 in the Regulatory Pathway That Couples GCN4 Expression to Amino Acid Availability in Saccharomyces cerevisiae
E. M. Hannig, N. P. Williams, R. C. Wek and A. G. Hinnebusch
Section on Molecular Genetics of Lower Eukaryotes, Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 Current address: Department of Molecular and Cell Biology, The University of Texas at Dallas, P.O. Box 830688, Mail Station FO3. 1, Richardson, Texas 75083-0688.
The GCN4 protein of S. cerevisiae is a transcriptional activator of amino acid biosynthetic genes which are subject to general amino acid control. GCN3, a positive regulator required for increased GCN4 expression in amino acid-starved cells, is thought to function by antagonism of one or more negative regulators encoded by GCD genes. We isolated gcn3(c) alleles that lead to constitutively derepressed expression of GCN4 and amino acid biosynthetic genes under its control. These mutations map in the protein-coding sequences and, with only one exception, do not increase the steady-state level of GCN3 protein. All of the gcn3(c) alleles lead to derepression of genes under the general control in the absence of GCN1 and GCN2, two other positive regulators of GCN4 expression. This finding suggests that GCN3 functions downstream from GCN1 and GCN2 in the general control pathway. In accord with this idea, constitutively derepressing alleles of GCN2 are greatly dependent on GCN3 for their derepressed phenotype. The gcn3(c) alleles that are least dependent on GCN1 and GCN2 for derepression cause slow-growth under nonstarvation conditions. In addition, all of the gcn3(c) alleles are less effective than wild-type GCN3 in overcoming the temperature-sensitive lethality associated with certain mutations in the negative regulator GCD2. These results suggest that activation of GCN3 positive regulatory function by the gcn3(c) mutations involves constitutive antagonism of GCD2 function, leading to reduced growth rates and derepression of GCN4 expression in the absence of amino acid starvation.
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