title: Dynamics of Cdk1 substrate specificity during the cell cycle.
abstract: Cdk specificity is determined by the intrinsic selectivity of the active site and by substrate docking sites on the cyclin subunit. There is a long-standing debate about the relative importance of these factors in the timing of Cdk1 substrate phosphorylation. We analyzed major budding yeast cyclins (the G1/S-cyclin Cln2, S-cyclin Clb5, G2/M-cyclin Clb3, and M-cyclin Clb2) and found that the activity of Cdk1 toward the consensus motif increased gradually in the sequence Cln2-Clb5-Clb3-Clb2, in parallel with cell cycle progression. Further, we identified a docking element that compensates for the weak intrinsic specificity of Cln2 toward G1-specific targets. In addition, Cln2-Cdk1 showed distinct consensus site specificity, suggesting that cyclins do not merely activate Cdk1 but also modulate its active-site specificity. Finally, we identified several Cln2-, Clb3-, and Clb2-specific Cdk1 targets. We propose that robust timing and ordering of cell cycle events depend on gradual changes in the substrate specificity of Cdk1.
authors.affiliation: Institute of Technology, University of Tartu, Tartu 50411, Estonia. mart.loog@ut.ee
authors.forename: Mardo
authors.initials: M
authors.lastname: Kõivomägi
authors.forename: Ervin
authors.initials: E
authors.lastname: Valk
authors.forename: Rainis
authors.initials: R
authors.lastname: Venta
authors.forename: Anna
authors.initials: A
authors.lastname: Iofik
authors.forename: Martin
authors.initials: M
authors.lastname: Lepiku
authors.forename: David O
authors.initials: DO
authors.lastname: Morgan
authors.forename: Mart
authors.initials: M
authors.lastname: Loog
mesh_terms: D020816:Amino Acid Motifs; D001665:Binding Sites; D016203:CDC2 Protein Kinase / Q000737:chemistry / Q000378:metabolism*; D002453:Cell Cycle; D016384:Consensus Sequence; D057927:Hydrophobic and Hydrophilic Interactions; D008954:Models, Biological; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D016203:CDC2 Protein Kinase