Differential control of Eg5-dependent centrosome separation by Plk1 and Cdk1

Smith, Ewan, Hegarat, Nadia, Vesely, Clare, Roseboom, Isaac, Larch, Christopher, Streicher, Hansjorg, Straatman, Kornelis, Flynn, Helen, Skehel, Mark, Hirota, Toru, Kuriyama, Ryoko and Hochegger, Helfrid (2011) Differential control of Eg5-dependent centrosome separation by Plk1 and Cdk1. EMBO Journal, 30 (11). pp. 2233-2245. ISSN 0261-4189

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Abstract

Cyclin-dependent kinase 1 (Cdk1) is thought to trigger centrosome separation in late G2 phase by phosphorylating the motor protein Eg5 at Thr927. However, the precise control mechanism of centrosome separation remains to be understood. Here, we report that in G2 phase polo-like kinase 1 (Plk1) can trigger centrosome separation independently of Cdk1. We find that Plk1 is required for both C-Nap1 displacement and for Eg5 localization on the centrosome. Moreover, Cdk2 compensates for Cdk1, and phosphorylates Eg5 at Thr927. Nevertheless, Plk1-driven centrosome separation is slow and staggering, while Cdk1 triggers fast movement of the centrosomes. We find that actin-dependent Eg5-opposing forces slow down separation in G2 phase. Strikingly, actin depolymerization, as well as destabilization of interphase microtubules (MTs), is sufficient to remove this obstruction and to speed up Plk1-dependent separation. Conversely, MT stabilization in mitosis slows down Cdk1-dependent centrosome movement. Our findings implicate the modulation of MT stability in G2 and M phase as a regulatory element in the control of centrosome separation.

Item Type: Article
Schools and Departments: School of Life Sciences > Chemistry
Subjects: Q Science
Depositing User: Ewan Smith
Date Deposited: 06 Feb 2012 19:06
Last Modified: 09 Oct 2012 13:41
URI: http://sro.sussex.ac.uk/id/eprint/19263
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