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  current news   Press   selected story    
     
  2nd June  
 

Inactivation of Cdh1 by synergistic action of Cdk1 and Polo kinase is necessary for proper assembly of mitotic spindle

 
 




Authors
Karen Crasta, Hong Hwa Lim, Thomas H. Giddings Jr, Mark Winey and Uttam Surana*

Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Republic of Singapore.
Correspondence should be addressed to Uttam Surana: mcbucs@imcb.a-star.edu.sg

Published in Nature Cell Biology, 25 May 2008, Vol 10: 665-675.

Abstract
Separation of duplicated centrosomes (spindle pole body or SPB in yeast) is a crucial step in the biogenesis of mitotic spindle. In vertebrate cells, 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 elucidated. In budding yeast, SPB separation also requires activated Cdk1 and the plus-end kinesins Cin8 (homologous to vertebrate Eg5) and Kip1. Here we report a novel role for polo kinase in the separation of SPBs. We show that adequate accumulation of Cin8 and Kip1 requires inactivation of anaphase-promoting complex-activator Cdh1 via sequential phosphorylation by Cdk1 and polo kinase. In this process Cdk1 acts as a priming kinase in that Cdk1-mediated phosphorylation creates a binding site for polo kinase which further phosphorylates Cdh1. Thus, Cdh1 inactivation by synergistic action of Cdk1 and polo kinase provides a new paradigm for inactivation of cell cycle effectors.

 
 


 
 

Figure & Legend: Mechanism for the regulation of centrosome separation involving Cdk1, Polo kinase, Cdh1, Acm1 and microtubule binding proteins Cin8 and Kip1.
E3 ubiquitin ligase-activator Cdh1 is a potent inhibitor of centrosome separation. For the assembly of a bipolar mitotic spindle Cdh1 must be inactivated during S phase to allow accumulation of microtubule binding proteins such as Cin8 (homolog of mammalian kinesin motor Eg5) which severe the intra-centrosomal bridge. Our results strongly suggest that Cdh1 inactivation requires synergistic phosphorylation by Cdk1 and Polo kinase. In this regulatory scheme, Cdk1 acts as a priming kinase for the Polo kinase. Further separation of SPBs for the assembly of a characteristic short spindle requires greater accumulation of these kinesin motors, mediated by Acm1 and Polo kinase.

For more information on Prof. Surana’s lab, Please Click here.