Cdk phosphorylation of the Ste11 transcription factor constrains differentiation-specific transcription to G1.
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Cdk phosphorylation of the Ste11 transcription factor constrains differentiation-specific transcription to G1. / Kjaerulff, Søren; Andersen, Nicoline Resen; Borup, Mia Trolle; Nielsen, Olaf.
In: Genes & Development, Vol. 21, No. 3, 2007, p. 347-59.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Cdk phosphorylation of the Ste11 transcription factor constrains differentiation-specific transcription to G1.
AU - Kjaerulff, Søren
AU - Andersen, Nicoline Resen
AU - Borup, Mia Trolle
AU - Nielsen, Olaf
N1 - Keywords: CDC2 Protein Kinase; Cell Differentiation; Cyclin-Dependent Kinases; DNA-Binding Proteins; G1 Phase; Gene Expression Regulation; Models, Biological; Phosphorylation; Schizosaccharomyces; Schizosaccharomyces pombe Proteins; Sex Differentiation; Transcription Factors; Transcription, Genetic; Ubiquitin
PY - 2007
Y1 - 2007
N2 - 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).
AB - 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).
U2 - 10.1101/gad.407107
DO - 10.1101/gad.407107
M3 - Journal article
C2 - 17289922
VL - 21
SP - 347
EP - 359
JO - Genes & Development
JF - Genes & Development
SN - 0890-9369
IS - 3
ER -
ID: 5626492