Mio depletion links mTOR regulation to Aurora A and Plk1 activation at mitotic centrosomes |
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| Authors: | Melpomeni Platani Laura Trinkle-Mulcahy Michael Porter A. Arockia Jeyaprakash William C. Earnshaw |
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| Affiliation: | 1.Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, Scotland, UK;2.Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H8M5, Canada;3.Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario K1H8M5, Canada;4.Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK |
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| Abstract: | Coordination of cell growth and proliferation in response to nutrient supply is mediated by mammalian target of rapamycin (mTOR) signaling. In this study, we report that Mio, a highly conserved member of the SEACAT/GATOR2 complex necessary for the activation of mTORC1 kinase, plays a critical role in mitotic spindle formation and subsequent chromosome segregation by regulating the proper concentration of active key mitotic kinases Plk1 and Aurora A at centrosomes and spindle poles. Mio-depleted cells showed reduced activation of Plk1 and Aurora A kinase at spindle poles and an impaired localization of MCAK and HURP, two key regulators of mitotic spindle formation and known substrates of Aurora A kinase, resulting in spindle assembly and cytokinesis defects. Our results indicate that a major function of Mio in mitosis is to regulate the activation/deactivation of Plk1 and Aurora A, possibly by linking them to mTOR signaling in a pathway to promote faithful mitotic progression. |
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