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Plk1 regulates mitotic Aurora A function through βTrCP-dependent degradation of hBora

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Abstract

Polo-like kinase 1 (Plk1) and Aurora A play key roles in centrosome maturation, spindle assembly, and chromosome segregation during cell division. Here we show that the functions of these kinases during early mitosis are coordinated through Bora, a partner of Aurora A first identified in Drosophila. Depletion of human Bora (hBora) results in spindle defects, accompanied by increased spindle recruitment of Aurora A and its partner TPX2. Conversely, hBora overexpression induces mislocalization of Aurora A and monopolar spindle formation, reminiscent of the phenotype seen in Plk1-depleted cells. Indeed, Plk1 regulates hBora. Following Cdk1-dependent recruitment, Plk1 triggers hBora destruction by phosphorylating a recognition site for \({\text{SCF}}^{{\text{ $ \beta $ - TrCP}}} \). Plk1 depletion or inhibition results in a massive accumulation of hBora, concomitant with displacement of Aurora A from spindle poles and impaired centrosome maturation, but remarkably, co-depletion of hBora partially restores Aurora A localization and bipolar spindle formation. This suggests that Plk1 controls Aurora A localization and function by regulating cellular levels of hBora.

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Acknowledgements

We thank Anja Wehner for excellent technical assistance and Xiuling Li and Stefan Hümmer for help with mass spectrometry and live-cell imaging. We are also grateful to Andrea Hutterer and Juergen A. Knoblich (IMBA, Vienna) for communicating results prior to publication and to Xiumin Yan, Francis Barr, Rüdiger Neef, Tobias Oelschlägel, and Thomas Mayer for helpful discussion. This work was supported by the Max Planck Society, the ‘Deutsche Forschungsgemeinschaft (SFB 646), and the ‘Fonds der Chemischen Industrie’. E.H.Y. Chan was supported by the Hong Kong Croucher Foundation.

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  1. Eunice H. Y. Chan

    Present address: Apoptosis and Proliferation Control Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln’s Inn Fields, London, WC2A 3PX, UK

  2. Herman H. W. Silljé

    Present address: Kiadis Pharma, Zernikepark 6-8, 9747 AN, Groningen, The Netherlands

Authors and Affiliations

  1. Department of Cell Biology, Max Planck Institute of Biochemistry, 82152, Martinsried, Germany

    Eunice H. Y. Chan, Anna Santamaria, Herman H. W. Silljé & Erich A. Nigg

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  1. Eunice H. Y. Chan
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Correspondence to Erich A. Nigg.

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Chan, E.H.Y., Santamaria, A., Silljé, H.H.W. et al. Plk1 regulates mitotic Aurora A function through βTrCP-dependent degradation of hBora. Chromosoma 117, 457–469 (2008). https://doi.org/10.1007/s00412-008-0165-5

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