The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae.
When yeast cells reach a critical size, they initiate bud formation, spindle pole body duplication, and DNA replication almost simultaneously. All three events depend on activation of Cdc28 protein kinase by the G1 cyclins Cln1, -2, and -3. We show that DNA replication also requires activation of Cdc28 by B-type (Clb) cyclins. A sextuple clb1-6 mutant arrests as multibudded G1 cells that resemble cells lacking the Cdc34 ubiquitin-conjugating enzyme. cdc34 mutants cannot enter S phase because they fail to destroy p40SIC1, which is a potent inhibitor of Clb but not Cln forms of the Cdc28 kinase. In wild-type cells, p40SIC1 protein appears at the end of mitosis and disappears shortly before S phase. Proteolysis of a cyclin-specific inhibitor of Cdc28 is therefore an essential aspect of the G1 to S phase transition.
Schwob
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I. M. P. Research Institute of Molecular Pathology, Vienna, Austria.
Böhm
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Mendenhall
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Nasmyth
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D064173:Anaphase-Promoting Complex-Cyclosome; D017489:CDC28 Protein Kinase, S cerevisiae / Q000037:antagonists & inhibitors / Q000502:physiology*; D002453:Cell Cycle; D019926:Cyclin B; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins / Q000502:physiology*; D005656:Fungal Proteins / Q000502:physiology*; D008025:Ligases / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000166:cytology*; D029701:Saccharomyces cerevisiae Proteins; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases
C076558:CLB5 protein, S cerevisiae; D019926:Cyclin B; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; D005656:Fungal Proteins; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C577449:CDC34 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D017489:CDC28 Protein Kinase, S cerevisiae; D008025:Ligases