Regulation of the transcription factor Gcn4 by Pho85 cyclin PCL5.
The yeast transcription factor Gcn4 is regulated by amino acid starvation at the levels of both protein synthesis and stability. Gcn4 degradation depends on the ubiquitination complex SCF(CDC4) and requires phosphorylation by the cyclin-dependent kinase Pho85. Here, we show that Pcl5 is the Pho85 cyclin specifically required for Gcn4 degradation. PCL5 is itself induced by Gcn4 at the level of transcription. However, even when PCL5 is constitutively overexpressed, Pho85-associated Gcn4 phosphorylation activity is reduced in starved cells and Gcn4 degradation is decreased. Under these conditions, the Pcl5 protein disappears because of rapid constitutive turnover. We suggest that, by virtue of its constitutive metabolic instability, Pcl5 may be a sensor of cellular protein biosynthetic capacity. The fact that PCL5 is transcriptionally induced in the presence of Gcn4 suggests that it is part of a homeostatic mechanism that reduces Gcn4 levels upon recovery from starvation.
Shemer
Revital
R
Department of Molecular Microbiology, B. Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel.
Meimoun
Ariella
A
Holtzman
Tsvi
T
Kornitzer
Daniel
D
D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D015966:Gene Expression Regulation, Fungal; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D016213:Cyclins; D004268:DNA-Binding Proteins; C461492:PCL5 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D011494:Protein Kinases; D018844:Cyclin-Dependent Kinases; C058605:PHO85 protein, S cerevisiae