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Centrosome-associated Chk1 prevents premature activation of cyclin-B-Cdk1 kinase

Krämer, Alwin and Mailand, Niels and Lukas, Claudia and Syljuåsen, Randi G. and Wilkinson, Christopher J. and Nigg, Erich A. and Bartek, Jiri and Lukas, Jiri. (2004) Centrosome-associated Chk1 prevents premature activation of cyclin-B-Cdk1 kinase. Nature cell biology, Vol. 6, H. 9. pp. 884-891.

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Official URL: http://edoc.unibas.ch/dok/A5249378

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Abstract

Entry into mitosis occurs after activation of Cdk1, resulting in chromosome condensation in the nucleus and centrosome separation, as well as increased microtubule nucleation activity in the cytoplasm. The active cyclin-B1-Cdk1 complex first appears at the centrosome, suggesting that the centrosome may facilitate the activation of mitotic regulators required for the commitment of cells to mitosis. However, the signalling pathways involved in controlling the initial activation of Cdk1 at the centrosome remain largely unknown. Here, we show that human Chk1 kinase localizes to interphase, but not mitotic, centrosomes. Chemical inhibition of Chk1 resulted in premature centrosome separation and activation of centrosome-associated Cdk1. Forced immobilization of kinase-inactive Chk1 to centrosomes also resulted in premature Cdk1 activation. Conversely, under such conditions wild-type Chk1 impaired activation of centrosome-associated Cdk1, thereby resulting in DNA endoreplication and centrosome amplification. Activation of centrosomal Cdk1 in late prophase seemed to be mediated by cytoplasmic Cdc25B, whose activity is controlled by centrosome-associated Chk1. These results suggest that centrosome-associated Chk1 shields centrosomal Cdk1 from unscheduled activation by cytoplasmic Cdc25B, thereby contributing to proper timing of the initial steps of cell division, including mitotic spindle formation.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum
05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Cell Biology (Nigg)
UniBasel Contributors:Nigg, Erich A.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:MacMillan
ISSN:1465-7392
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:11 Oct 2012 15:16
Deposited On:22 Mar 2012 13:17

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