The WD protein Cpc2p is required for repression of Gcn4 protein activity in yeast in the absence of amino-acid starvation

The CPC2 gene of the budding yeast Saccharomyces cerevisiae encodes a G bet a-like WD protein which is involved in regulating the activity of the gener al control activator Gcn4p. The CPC2 gene encodes a premRNA which is splice d and constitutively expressed in the presence or absence of amino acids. L oss of CPC2 gene function suppresses a deletion of the GCN2 gene encoding t he general control sensor kinase, but not a deletion in the GCN4 gene. The resulting phenotype has resistance against amino-acid analogues. The Neuros pora crassa cpc-2 and the rat RACK1 genes are homologues of CPC2 that compl ement the yeast cpc2 deletion. The cpc2 Delta mutation leads to increased t ranscription of Gcn4p-dependent genes under non-starvation conditions witho ut increasing GCN4 expression or the DNA binding activity of Gcn4p. Cpc2p-m ediated transcriptional repression requires the Gcn4p transcriptional activ ator and a Gcn4p recognition element in the target promoter. Frameshift mut ations resulting in a shortened G beta-like protein cause a different pheno type that has sensitivity against amino-acid analogues similar to a gcn2 de letion. Cpc2p seems to be part of an additional control of Gcn4p activity, independent of its translational regulation.