Cdk phosphorylation of the Ste11 transcription factor constrains differentiation-specific transcription to G1.
Eukaryotic cells normally differentiate from G(1); here we investigate the mechanism preventing expression of differentiation-specific genes outside G(1). In fission yeast, induction of the transcription factor Ste11 triggers sexual differentiation. We find that Ste11 is only active in G(1) when Cdk activity is low. In the remaining part of the cell cycle, Ste11 becomes Cdk-phosphorylated at Thr 82 (T82), which inhibits its DNA-binding activity. Since the ste11 gene is autoregulated and the Ste11 protein is highly unstable, this Cdk switch rapidly extinguishes Ste11 activity when cells enter S phase. When we mutated T82 to aspartic acid, mimicking constant phosphorylation, cells no longer underwent differentiation. Conversely, changing T82 to alanine rendered Ste11-controlled transcription constitutive through the cell cycle, and allowed mating from S phase with increased frequency. Thus, Cdk phosphorylation mediates periodic expression of Ste11 and its target genes, and we suggest this to be part of the mechanism restricting differentiation to G(1).
Kjaerulff
Søren
S
Institute of Molecular Biology and Physiology, University of Copenhagen, DK-1353 Copenhagen K, Denmark.
Andersen
Nicoline Resen
NR
Borup
Mia Trolle
MT
Nielsen
Olaf
O
D016203:CDC2 Protein Kinase / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D016193:G1 Phase; D005786:Gene Expression Regulation; D008954:Models, Biological; D010766:Phosphorylation; D012568:Schizosaccharomyces / Q000166:cytology; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D012733:Sex Differentiation; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism
D004268:DNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; D025801:Ubiquitin; C071596:ste11 protein, S pombe; D016203:CDC2 Protein Kinase; D018844:Cyclin-Dependent Kinases; C469447:cdc2 protein, S pombe