title: A quantitative model for ordered Cdk substrate dephosphorylation during mitotic exit.
abstract: After sister chromatid splitting at anaphase onset, exit from mitosis comprises an ordered series of events. Dephosphorylation of numerous mitotic substrates, which were phosphorylated by cyclin-dependent kinase (Cdk), is thought to bring about mitotic exit, but how temporal ordering of mitotic exit events is achieved is poorly understood. Here, we show, using budding yeast, that dephosphorylation of Cdk substrates involved in sequential mitotic exit events occurs with ordered timing. We test different models of how ordering might be achieved by modulating Cdk and Cdk-counteracting phosphatase Cdc14 activities in vivo, as well as by kinetic analysis of Cdk substrate phosphorylation and dephosphorylation in vitro. Our results suggest that the gradual change of the phosphatase to kinase ratio over the course of mitotic exit is read out by Cdk substrates that respond by dephosphorylation at distinct thresholds. This provides an example and a mechanistic explanation for a quantitative model of cell-cycle progression.
authors.affiliation: Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, London WC2A 3LY, UK.
authors.forename: Céline
authors.initials: C
authors.lastname: Bouchoux
authors.forename: Frank
authors.initials: F
authors.lastname: Uhlmann
mesh_terms: D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D008938:Mitosis; D008954:Models, Biological; D010744:Phosphoric Monoester Hydrolases; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: C074860:CDC14 protein, S cerevisiae; C093749:CLB2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D019926:Cyclin B; D029701:Saccharomyces cerevisiae Proteins; D018844:Cyclin-Dependent Kinases; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases