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Article
Subject Categories: Cell Cycle
The EMBO Journal (2006) 25, 2551–2563, doi:10.1038/sj.emboj.7601136
Published online 11 May 2006
Cdk1 regulates centrosome separation by restraining proteolysis of microtubule-associated proteins
Karen Crasta1, Phillips Huang1, Garry Morgan2, Mark Winey2 and Uttam Surana1
1 Institute of Molecular and Cell Biology, Proteos, Singapore
2 Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO, USA

To whom correspondence should be addressed
Uttam Surana, Institute of Molecular and Cell Biology, Proteos, 61, Biopolis Drive, Singapore 138673, Singapore. Tel.: +65 6586 9503; Fax: +65 6779 1117; E-mail: mcbucs@imcb.a-star.edu.sg

Received 10 November 2005; Accepted 18 April 2006; Published online 11 May 2006.
Abstract
In yeast, separation of duplicated spindle pole bodies (SPBs) (centrosomes in higher eukaryotes) is an indispensable step in the assembly of mitotic spindle and is triggered by severing of the bridge that connects the sister SPBs. This process requires Cdk1 (Cdc28) activation by Tyrosine 19 dephosphorylation. We show that cells that fail to activate Cdk1 are devoid of spindles due to persistently active APCCdh1, which targets microtubule-associated proteins Cin8, Kip1 and Ase1 for degradation. Tyrosine 19 dephosphorylation of Cdk1 is necessary to specifically prevent proteolysis of these proteins. Interestingly, SPB separation is dependent on the microtubule-bundling activity of Cin8 but not on its motor function. Since ectopic expression of proteolysis-resistant Cin8, Kip1 or Ase1 is sufficient for SPB separation even in the absence of Cdc28-Clb activity, we suggest that stabilization of these mechanical force-generating proteins is the predominant role of Cdc28-Clb in centrosome separation.
Keywords: Cdh1, centrosomes, mitosis, spindle, SPB
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