title: Aurora A kinase (AURKA) in normal and pathological cell division.
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.
authors.affiliation: Program in Developmental Therapeutics, Fox Chase Cancer Center, W406, 333 Cottman Ave., Philadelphia, PA 19111, USA.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Nikonova
authors.forename: Igor
authors.initials: I
authors.lastname: Astsaturov
authors.forename: Ilya G
authors.initials: IG
authors.lastname: Serebriiskii
authors.forename: Roland L
authors.initials: RL
authors.lastname: Dunbrack
authors.forename: Erica A
authors.initials: EA
authors.lastname: Golemis
mesh_terms: D000818:Animals; D064096:Aurora Kinase A; D064127:Aurora Kinases; D002455:Cell Division; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D060066:Protein Interaction Maps; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases