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Insights into the non-mitotic functions of Aurora kinase A: more than just cell division

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Abstract

AURKA is a serine/threonine kinase overexpressed in several cancers. Originally identified as a protein with multifaceted roles during mitosis, improvements in quantitative microscopy uncovered several non-mitotic roles as well. In physiological conditions, AURKA regulates cilia disassembly, neurite extension, cell motility, DNA replication and senescence programs. In cancer-like contexts, AURKA actively promotes DNA repair, it acts as a transcription factor, promotes cell migration and invasion, and it localises at mitochondria to regulate mitochondrial dynamics and ATP production. Here we review the non-mitotic roles of AURKA, and its partners outside of cell division. In addition, we give an insight into how structural data and quantitative fluorescence microscopy allowed to understand AURKA activation and its interaction with new substrates, highlighting future developments in fluorescence microscopy needed to better understand AURKA functions in vivo. Last, we will recapitulate the most significant AURKA inhibitors currently in clinical trials, and we will explore how the non-mitotic roles of the kinase may provide new insights to ameliorate current pharmacological strategies against AURKA overexpression.

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Acknowledgements

We would like to thank C. Prigent, R. Le Borgne, F. Sizaire and EB Gökerküçuk for helpful discussions and feedback concerning AURKA functions and FRET biosensors, and Y. Gautier for help with graphical art. This work was supported by the Centre Nationale de la Recherche Scientifique (CNRS), by the University of Rennes, by the Ligue Contre le Cancer Comité d’Ille et Vilaine et Comité des Côtes d’Armor to G.B. and by the Comité d’Ille et Vilaine, Comité du Maine et Loire et Comité de la Sarthe to MT.

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    Giulia Bertolin & Marc Tramier

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Bertolin, G., Tramier, M. Insights into the non-mitotic functions of Aurora kinase A: more than just cell division. Cell. Mol. Life Sci. 77, 1031–1047 (2020). https://doi.org/10.1007/s00018-019-03310-2

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