title: Inactivation of Cdh1 by synergistic action of Cdk1 and polo kinase is necessary for proper assembly of the mitotic spindle.
abstract: Separation of duplicated centrosomes (spindle-pole bodies or SPBs in yeast) is a crucial step in the biogenesis of the mitotic spindle. In vertebrates, centrosome separation requires the BimC family kinesin Eg5 and the activities of Cdk1 and polo kinase; however, the roles of these kinases are not fully understood. In Saccharomyces cerevisiae, SPB separation also requires activated Cdk1 and the plus-end kinesins Cin8 (homologous to vertebrate Eg5) and Kip1. Here we report that polo kinase has a role in the separation of SPBs. We show that adequate accumulation of Cin8 and Kip1 requires inactivation of the anaphase-promoting complex-activator Cdh1 through sequential phosphorylation by Cdk1 and polo kinase. In this process, Cdk1 functions as a priming kinase in that Cdk1-mediated phosphorylation creates a binding site for polo kinase,which further phosphorylates Cdh1. Thus, Cdh1 inactivation through the synergistic action of Cdk1 and polo kinase provides a new model for inactivation of cell-cycle effectors.
authors.affiliation: Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), 61, Biopolis Drive, Proteos, Singapore.
authors.forename: Karen
authors.initials: K
authors.lastname: Crasta
authors.forename: Hong Hwa
authors.initials: HH
authors.lastname: Lim
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Giddings
authors.forename: Mark
authors.initials: M
authors.lastname: Winey
authors.forename: Uttam
authors.initials: U
authors.lastname: Surana
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D017489:CDC28 Protein Kinase, S cerevisiae / Q000378:metabolism; D064200:Cdh1 Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008954:Models, Biological; D008957:Models, Genetic; D020409:Molecular Motor Proteins; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D008941:Spindle Apparatus; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism; D000097869:Polo-Like Kinase 1
chemical_list: D064173:Anaphase-Promoting Complex-Cyclosome; D016203:CDC2 Protein Kinase; D017489:CDC28 Protein Kinase, S cerevisiae; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; D051360:Cyclin-Dependent Kinase 5; D008869:Microtubule-Associated Proteins; D020409:Molecular Motor Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D000097869:Polo-Like Kinase 1; C516306:Acm1 protein, S cerevisiae; C577583:CDH1 protein, S cerevisiae; C431747:KIP1 protein, S cerevisiae