Overexpression of the Aurora kinase A (AURKA) is oncogenic in many tumors. Many studies of AURKA have focused on activities of this kinase in mitosis, and elucidated the mechanisms by which AURKA activity is induced at the G2/M boundary through interactions with proteins such as TPX2 and NEDD9. These studies have informed the development of small molecule inhibitors of AURKA, of which a number are currently under preclinical and clinical assessment. While the first activities defined for AURKA were its control of centrosomal maturation and organization of the mitotic spindle, an increasing number of studies over the past decade have recognized a separate biological function of AURKA, in controlling disassembly of the primary cilium, a small organelle protruding from the cell surface that serves as a signaling platform. Importantly, these activities require activation of AURKA in early G1, and the mechanisms of activation are much less well defined than those in mitosis. A better understanding of the control of AURKA activity and the role of AURKA at cilia are both important in optimizing the efficacy and interpreting potential downstream consequences of AURKA inhibitors in the clinic. We here provide a current overview of proteins and mechanisms that have been defined as activating AURKA in G1, based on the study of ciliary disassembly.
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February 2017
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Cover Image
The surface of the catalytic subunit of protein phosphatase PP1 (central 3D-structure) has many binding sites for regulatory proteins that are embedded in regulatory networks (coloured circles linked by lines). Please see pp. 89–99 for more information. Image provided by Mathieu Bollen.
Review Article|
February 15 2017
Mechanisms for nonmitotic activation of Aurora-A at cilia
Vladislav Korobeynikov;
Vladislav Korobeynikov
1Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, U.S.A.
2Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, U.S.A.
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Alexander Y. Deneka;
Alexander Y. Deneka
1Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, U.S.A.
3Kazan Federal University, Kazan 420000, Russian Federation
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Erica A. Golemis
1Molecular Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, U.S.A.
Correspondence: Erica A. Golemis (erica.golemis@fccc.edu)
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Publisher: Portland Press Ltd
Received:
June 01 2016
Revision Received:
October 19 2016
Accepted:
October 24 2016
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society
2017
Biochem Soc Trans (2017) 45 (1): 37–49.
Article history
Received:
June 01 2016
Revision Received:
October 19 2016
Accepted:
October 24 2016
Citation
Vladislav Korobeynikov, Alexander Y. Deneka, Erica A. Golemis; Mechanisms for nonmitotic activation of Aurora-A at cilia. Biochem Soc Trans 8 February 2017; 45 (1): 37–49. doi: https://doi.org/10.1042/BST20160142
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