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PMID: 16688214 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cdk1 regulates centrosome separation by restraining proteolysis of microtubule-associated proteins.

The EMBO journal ·Vol. 25 ·No. 11 ·2006-06-07 ·Pages 2551-63

Crasta K, Huang P, Morgan G, Winey M, Surana U

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.

MeSH Terms
CDC2 Protein Kinase/genetics,metabolism CDC28 Protein Kinase, S cerevisiae/genetics,metabolism Cdh1 Proteins Cell Cycle/physiology Centrosome/metabolism Enzyme Activation Kinesins Microtubule-Associated Proteins/genetics,metabolism Molecular Motor Proteins Proteasome Endopeptidase Complex/metabolism Saccharomyces cerevisiae/cytology,genetics,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism Spindle Apparatus/metabolism
Chemicals
Ase1 protein, S cerevisiae CIN8 protein, S cerevisiae Cdh1 Proteins KIP1 protein, S cerevisiae Microtubule-Associated Proteins Molecular Motor Proteins Saccharomyces cerevisiae Proteins CDC2 Protein Kinase CDC28 Protein Kinase, S cerevisiae Proteasome Endopeptidase Complex Kinesins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Crasta Karen
Institute of Molecular and Cell Biology, Proteos, Singapore.
Huang Phillips
Morgan Garry
Winey Mark
Surana Uttam
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7601136
Published
2006-06-07
Epub
2006-00-11
Pages
2551-63
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1478175
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7601136 PMC Full Text View journal details
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