Fission yeast pheromone blocks S-phase by inhibiting the G1 cyclin B-p34cdc2 kinase.
Yeast pheromones block cell cycle progression in G1 in order to prepare mating partners for conjugation. We have investigated the mechanism underlying pheromone-induced G1 arrest in the fission yeast Schizosaccharomyces pombe. We find that the G1-specific transcription factor p65cdc10-p72res1/sct1 which controls the expression of S-phase genes is fully activated in pheromone, unlike the analogous control in budding yeast. In contrast, the G1 function of p34cdc2 acting after activation of the G1-specific transcription is blocked. Pheromone inhibits the p34cdc2 kinase associated with both the G1-specific B-type cyclin p45cig2 and the B-type cyclin p56cdc13 and overexpression of p45cig2 or p47cdc13delta90 overcomes the pheromone-induced G1 arrest. G1 arrest is compromised in enlarged cells. We suggest that onset of S-phase is controlled by pheromone inhibiting the B-cyclin-associated kinase in G1, and that increasing cell size contributes to the mechanism for pheromone adaptation. Thus, pheromone in fission and budding yeast acts similarly in inhibiting the G1 cyclin-dependent kinase (CDK), but differs in its effects on the G1/S transcriptional control, suggesting that inhibition of CDKs may be a more general mechanism for the control of G1 progression compared with G1/S transcriptional control.
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Cell Cycle Laboratory, Imperial Cancer Research Fund, London, UK.
Nurse
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D015152:Blotting, Northern; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002452:Cell Count / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects; D019926:Cyclin B; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D004247:DNA / Q000032:analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D006918:Hydroxyurea / Q000494:pharmacology; D010675:Pheromones / Q000494:pharmacology*; D021382:Protein Sorting Signals / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects* / Q000235:genetics; D012568:Schizosaccharomyces / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins; D013696:Temperature; D014157:Transcription Factors / Q000378:metabolism / Q000494:pharmacology
D019926:Cyclin B; D016213:Cyclins; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D010675:Pheromones; D021382:Protein Sorting Signals; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C085847:map2 protein, S pombe; D004247:DNA; D016203:CDC2 Protein Kinase; D018844:Cyclin-Dependent Kinases; D006918:Hydroxyurea