title: Swe1 regulation and transcriptional control restrict the activity of mitotic cyclins toward replication proteins in Saccharomyces cerevisiae.
abstract: Cyclin-dependent kinases (CDKs) drive the cell cycle through the phosphorylation of substrates that function in genome duplication and cell division. The existence of multiple cyclin subunits and their distinct cell cycle-regulated expression suggests that cyclins impart unique specificities to CDK-substrate interactions that are critical for normal cellular function. This study shows that the combination of early cell cycle expression and deletion of the CDK inhibitor Saccharomyces Wee1 (Swe1) enables the mitotic B-type (Clb) cyclins Clb2, Clb3, and Clb4 of Saccharomyces cerevisiae to initiate S phase with similar effectiveness as the S-phase cyclin Clb5. Although in vivo analysis indicates preferential phosphorylation of a replication substrate by Clb5-Cdk1, this difference is relatively minor compared with the impact of transcriptional control and Swe1 regulation. Indeed, early expressed Clb2-Cdk1 can activate all essential Clb-Cdk substrates in a strain lacking all other Clbs and Swe1. Thus, Swe1 regulation and expression timing are key mechanisms that sequester the broad activity of Clb2-Cdk1 from critical substrates. Furthermore, the ability of Swe1 to inhibit the activity of different B-type cyclins in replication initiation correlates with the normal expression timing of those cyclins, with no apparent in vivo inhibition of Clb5 and Clb6, moderate inhibition of Clb3 and Clb4, and strong inhibition of Clb2. Hence, Swe1 appears to reinforce the temporal activity of cyclins established through transcriptional control. The conserved nature of CDK function suggests that similar mechanisms regulate CDK specificity in multicellular organisms.
authors.affiliation: Molecular and Computational Biology Program, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-2910, USA.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Hu
authors.forename: Oscar M
authors.initials: OM
authors.lastname: Aparicio
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics*; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D008938:Mitosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D016213:Cyclins; D029701:Saccharomyces cerevisiae Proteins; C099685:SWE1 protein, S cerevisiae; D011505:Protein-Tyrosine Kinases; D018844:Cyclin-Dependent Kinases