Cln3 activates G1-specific transcription via phosphorylation of the SBF bound repressor Whi5.
G1-specific transcriptional activation by Cln3/CDK initiates the budding yeast cell cycle. To identify targets of Cln3/CDK, we analyzed the SBF and MBF transcription factor complexes by multidimensional protein interaction technology (MudPIT). Whi5 was identified as a stably bound component of SBF but not MBF. Inactivation of Whi5 leads to premature expression of G1-specific genes and budding, whereas overexpression retards those processes. Whi5 inactivation bypasses the requirement for Cln3 both for transcriptional activation and cell cycle initiation. Whi5 associates with G1-specific promoters via SBF during early G1 phase, then dissociates coincident with transcriptional activation. Dissociation of Whi5 is promoted by Cln3 in vivo. Cln/CDK phosphorylation of Whi5 in vitro promotes its dissociation from SBF complexes. Mutation of putative CDK phosphorylation sites, at least five of which are phosphorylated in vivo, strongly reduces SBF-dependent transcription and delays cell cycle initiation. Like mammalian Rb, Whi5 is a G1-specific transcriptional repressor antagonized by CDK.
Pubmed ID: 15210110 RIS Download
Amino Acid Sequence | Amino Acid Substitution | Cell Size | Chromatin | Consensus Sequence | Cyclins | G1 Phase | Gene Expression Regulation, Fungal | Models, Genetic | Molecular Sequence Data | Phosphorylation | Precipitin Tests | Promoter Regions, Genetic | Repressor Proteins | Reverse Transcriptase Polymerase Chain Reaction | Saccharomyces cerevisiae | Saccharomyces cerevisiae Proteins | Transcription Factors | Transcription, Genetic | Transcriptional Activation