Interdomain allosteric regulation of Polo kinase by Aurora B and Map205 is required for cytokinesis |
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| Authors: | David Kachaner Xavier Pinson Khaled Ben El Kadhi Karine Normandin Lama Talje Hugo Lavoie Guillaume Lépine Sébastien Carréno Benjamin H. Kwok Gilles R. Hickson Vincent Archambault |
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| Affiliation: | 1.Institut de Recherche en Immunologie et en Cancérologie, 2.Départment de Biochimie et Médecine Moléculaire, 3.Centre Hospitalier Universitaire Sainte-Justine, 4.Département de Pathologie et de Biologie Cellulaire, 5.Département de Médecine, Université de Montréal, Montréal, Québec H3T 1J4, Canada |
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| Abstract: | Drosophila melanogaster Polo and its human orthologue Polo-like kinase 1 fulfill essential roles during cell division. Members of the Polo-like kinase (Plk) family contain an N-terminal kinase domain (KD) and a C-terminal Polo-Box domain (PBD), which mediates protein interactions. How Plks are regulated in cytokinesis is poorly understood. Here we show that phosphorylation of Polo by Aurora B is required for cytokinesis. This phosphorylation in the activation loop of the KD promotes the dissociation of Polo from the PBD-bound microtubule-associated protein Map205, which acts as an allosteric inhibitor of Polo kinase activity. This mechanism allows the release of active Polo from microtubules of the central spindle and its recruitment to the site of cytokinesis. Failure in Polo phosphorylation results in both early and late cytokinesis defects. Importantly, the antagonistic regulation of Polo by Aurora B and Map205 in cytokinesis reveals that interdomain allosteric mechanisms can play important roles in controlling the cellular functions of Plks. |
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