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Choice of Plk1 docking partners during mitosis and cytokinesis is controlled by the activation state of Cdk1

Abstract

Spatial and temporal coordination of polo-like kinase 1 (Plk1) activity is necessary for mitosis and cytokinesis, and this is achieved through binding to phosphorylated docking proteins with distinct subcellular localizations1,2,3,4. Although cyclin-dependent kinase 1 (Cdk1) creates these phosphorylated docking sites in metaphase1,2, a general principle that explains how Plk1 activity is controlled in anaphase after Cdk1 inactivation is lacking. Here, we show that the microtubule-associated protein regulating cytokinesis (PRC1) is an anaphase-specific binding partner for Plk1, and that this interaction is required for cytokinesis. In anaphase, Plk1 creates its own docking site on PRC1, whereas in metaphase Cdk1 phosphorylates PRC1 adjacent to this docking site and thereby prevents binding of Plk1. Mutation of these Cdk1-sites results in a form of PRC1 that prematurely recruits Plk1 to the spindle during prometaphase and blocks mitotic progression. The activation state of Cdk1, therefore, controls the switch of Plk1 localization from centrosomes and kinetochores during metaphase, to the central spindle during anaphase.

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Figure 1: PRC1 is a direct binding partner of Plk1 at the central spindle.
Figure 2: Plk1 localization to the central spindle is mediated by PRC1-2.
Figure 3: A Plk1 docking site at Ser 601/Thr 602 of PRC1 is required for cytokinesis.
Figure 4: PRC1 is an anaphase specific target of Plk1.
Figure 5: Phosphorylation by Cdk1 reduces binding of PRC1 to Plk1 in metaphase.

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Acknowledgements

We thank R. Körner for help with protein identification and phosphorylation site mapping by mass spectrometry. The Max-Planck Society supports research in the groups of F.A.B. and E.A.N. E.A.N. acknowledges support from the “Fonds der chemischen Industrie”.

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Authors and Affiliations

Authors

Contributions

R.N., H.S. and F.A.B. identified PRC1 as aPLK1-binding protein. R.N. and F.A.B. designed and performed the experiments to characterize the interaction of PRC1 with Plk1, and to determine the function of this interaction. U.G. analysed the differential interaction of PRC1 with KIF4 and Plk1. X.L. performed the mass spectrometry used to identify PRC1 and Plk1. R.K. developed and characterized the phosphospecific antibodies to PRC1. F.A.B. wrote the manuscript and directed the work. All authors discussed the results and commented on the manuscript.

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Correspondence to Francis A. Barr.

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The authors declare no competing financial interests.

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Supplementary Figures S1, S2, S3, S4 and S5 (PDF 305 kb)

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Neef, R., Gruneberg, U., Kopajtich, R. et al. Choice of Plk1 docking partners during mitosis and cytokinesis is controlled by the activation state of Cdk1. Nat Cell Biol 9, 436–444 (2007). https://doi.org/10.1038/ncb1557

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