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

2012; Springer Nature; Volume: 70; Issue: 4 Linguagem: Inglês

10.1007/s00018-012-1073-7

1420-9071

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

Plant nutrient uptake and metabolism

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.