title: Differential control of Eg5-dependent centrosome separation by Plk1 and Cdk1.
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.
authors.affiliation: Genome Damage and Stability Centre, University of Sussex, Brighton, UK.
authors.forename: Ewan
authors.initials: E
authors.lastname: Smith
authors.forename: Nadia
authors.initials: N
authors.lastname: Hégarat
authors.forename: Clare
authors.initials: C
authors.lastname: Vesely
authors.forename: Isaac
authors.initials: I
authors.lastname: Roseboom
authors.forename: Chris
authors.initials: C
authors.lastname: Larch
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Streicher
authors.forename: Kornelis
authors.initials: K
authors.lastname: Straatman
authors.forename: Helen
authors.initials: H
authors.lastname: Flynn
authors.forename: Mark
authors.initials: M
authors.lastname: Skehel
authors.forename: Toru
authors.initials: T
authors.lastname: Hirota
authors.forename: Ryoko
authors.initials: R
authors.lastname: Kuriyama
authors.forename: Helfrid
authors.initials: H
authors.lastname: Hochegger
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins; D016547:Kinesins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C470243:KIF11 protein, human