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Aurora A kinase (AURKA) in normal and pathological cell division

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Abstract

Temporally and spatially controlled activation of the Aurora A kinase (AURKA) regulates centrosome maturation, entry into mitosis, formation and function of the bipolar spindle, and cytokinesis. Genetic amplification and mRNA and protein overexpression of Aurora A are common in many types of solid tumor, and associated with aneuploidy, supernumerary centrosomes, defective mitotic spindles, and resistance to apoptosis. These properties have led Aurora A to be considered a high-value target for development of cancer therapeutics, with multiple agents currently in early-phase clinical trials. More recently, identification of additional, non-mitotic functions and means of activation of Aurora A during interphase neurite elongation and ciliary resorption have significantly expanded our understanding of its function, and may offer insights into the clinical performance of Aurora A inhibitors. Here we review the mitotic and non-mitotic functions of Aurora A, discuss Aurora A regulation in the context of protein structural information, and evaluate progress in understanding and inhibiting Aurora A in cancer.

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Acknowledgments

The authors were supported by R01s CA63366 and CA113342 (to EAG); by NIH R21 CA-164205 and 1K22CA-160725 (to IA); NIH R01 GM84453 (to RLD); and NIH core grant CA-06927, the Commonwealth of Pennsylvania, and the Pew Charitable Fund (to Fox Chase Cancer Center). The authors apologize for not being able to include discussion of additional relevant Aurora-A-related studies, because of the length limitations of this article.

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  1. Program in Developmental Therapeutics, Fox Chase Cancer Center, W406, 333 Cottman Ave., Philadelphia, PA, 19111, USA

    Anna S. Nikonova, Igor Astsaturov, Ilya G. Serebriiskii, Roland L. Dunbrack Jr. & Erica A. Golemis

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  1. Anna S. Nikonova
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Nikonova, A.S., Astsaturov, I., Serebriiskii, I.G. et al. Aurora A kinase (AURKA) in normal and pathological cell division. Cell. Mol. Life Sci. 70, 661–687 (2013). https://doi.org/10.1007/s00018-012-1073-7

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