Article abstract
Nature Cell Biology 10, 665 - 675 (2008)
Published online: 25 May 2008 | doi:10.1038/ncb1729
Inactivation of Cdh1 by synergistic action of Cdk1 and polo kinase is necessary for proper assembly of the mitotic spindle
Karen Crasta1, Hong Hwa Lim1, Thomas H. Giddings, Jr2, Mark Winey2 & Uttam Surana1
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.
- Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), 61, Biopolis Drive, Proteos, Singapore 138673.
- Department of Molecular, Cellular and Developmental Biology, University of Colorado, 347 UCB, Boulder, CO 80309-0347, USA.
Correspondence to: Uttam Surana1 e-mail: mcbucs@imcb.a-star.edu.sg
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