AIP regulates stability of Aurora-A at early mitotic phase coordinately with GSK-3β

Katsumi, Fumoto and Pui, Ching Lee and Hideyuki, Saya and Akira, Kikuchi (2008) AIP regulates stability of Aurora-A at early mitotic phase coordinately with GSK-3β. Oncogene, 27 (32). pp. 4478-4487. ISSN 0950-9232

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Official URL: http://dx.doi.org/10.1038/onc.2008.92

Abstract

Glycogen synthase kinase-3 (GSK-3β) regulates microtubule dynamics and cellular polarity through phosphorylating various microtubule associating proteins and plus-end tracking proteins. Although it was also reported that GSK-3β is inactivated by protein kinase B at the spindle poles, functions and targets of GSK-3β in the mitotic phase are unknown. Here, we identified Aurora-A-interacting protein (AIP), a negative regulator of Aurora-A, as a binding partner of GSK-3β. AIP was colocalized with Aurora-A and GSK-3β to the spindle poles in metaphase, and its depletion in cells stabilized and activated Aurora-A in early mitotic phase and caused mitotic cell arrest. Treatment of the cells with a GSK-3β inhibitor reduced the protein level of Aurora-A and this reduction was suppressed by AIP knockdown. AIP was phosphorylated by GSK-3β, and an AIP mutant in which the GSK-3β phosphorylation site was mutated could bind and downregulate Aurora-A more efficiently. These results suggest that GSK-3β modulates the early mitotic Aurora-A level through binding and phosphorylating AIP. © 2008 Macmillan Publishers Limited All rights reserved.

Item Type:Article
Uncontrolled Keywords:AIP, Aurora, Cell cycle, GSK-3β, Mitosis
Subjects:?? QH426-470 ??
Divisions:SCHOOL > School of Science and Technology
ID Code:2669
Deposited By:IR Admin
Deposited On:04 Apr 2011 14:53
Last Modified:17 Feb 2015 15:36

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