Cyclin B proteolysis and the cyclin-dependent kinase inhibitor rum1p are required for pheromone-induced G1 arrest in fission yeast.
The blocking of G1 progression by fission yeast pheromones requires inhibition of the cyclin-dependent kinase cdc2p associated with the B-cyclins cdc13p and cig2p. We show that cyclosome-mediated degradation of cdc13p and cig2p is necessary for down-regulation of B-cyclin-associated cdc2p kinase activity and for phermone-induced G1 arrest. The cyclin-dependent kinase inhibitor rum1p is also required to maintain this G1 arrest; it binds both cdc13p and cig2p and is specifically required for cdc13p proteolysis. We propose that rum1p acts as an adaptor targeting cdc13p for degradation by the cyclosome. In contrast, the cig2p-cdc2p kinase can be down-regulated, and the cyclin cig2p can be proteolyzed independently of rum1p. We suggest that pheromone signaling inhibits the cig2p-cdc2p kinase, bringing about a transient G1 arrest. As a consequence, rum1p levels increase, thus inhibiting and inducing proteolysis of the cdc13p-cdc2p kinase; this is necessary to maintain G1 arrest. We have also shown that pheromone-induced transcription occurs only in G1 and is independent of rum1p.
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Department of Physiology, University of California, San Francisco, San Francisco, California, 94143-0444, USA.
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D000818:Animals; D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins; D019926:Cyclin B / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010675:Pheromones / Q000494:pharmacology*; D011817:Rabbits; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors / Q000494:pharmacology*; D014158:Transcription, Genetic
D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; D018797:Cell Cycle Proteins; C080328:Cig2 protein, S pombe; D019926:Cyclin B; D016213:Cyclins; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; C577354:NUC2 protein, S pombe; D009687:Nuclear Proteins; C085846:P-factor, S pombe; D010675:Pheromones; C086077:Rum1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; D016203:CDC2 Protein Kinase; D018844:Cyclin-Dependent Kinases; D010450:Endopeptidases