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

Oncogene volume 27, pages 4478–4487 (2008)Cite this article

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.

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Acknowledgements

We thank Dr T Urano for providing antibody. This work was supported by Grants-in-Aid for Scientific Research and for Scientific Research on Priority Areas from the Ministry of Education, Science, and Culture, Japan (2004, 2005, 2006, and 2007). PCL was supported by a post-doctoral fellowship from the Japan Society for the Promotion of Science (JSPS).

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Author notes

  1. P-C Lee

    Present address: 4Current address: School of Science and Technology, University Malaysia Sabah, Kota Kinabalu, Sabah 88450, Malaysia.,

  2. K Fumoto and P-C Lee: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan

    K Fumoto, P-C Lee & A Kikuchi

  2. Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan

    H Saya

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  1. K Fumoto
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Correspondence to A Kikuchi.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Fumoto, K., Lee, PC., Saya, H. et al. AIP regulates stability of Aurora-A at early mitotic phase coordinately with GSK-3β. Oncogene 27, 4478–4487 (2008). https://doi.org/10.1038/onc.2008.92

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