Cdk phosphorylation of the Ste11 transcription factor constrains differentiation-specific transcription to G₁

Abstract

Eukaryotic cells normally differentiate from G₁; here we investigate the mechanism preventing expression of differentiation-specific genes outside G₁. In fission yeast, induction of the transcription factor Ste11 triggers sexual differentiation. We find that Ste11 is only active in G₁ 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 G₁.

Keywords

• Cell cycle
• differentiation
• Cdk
• Ste11
• S. pombe