Aurora kinase A

Definition:

Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for normal spindle positioning during mitosis and for the localization of NUMA1 and DCTN1 to the cell cortex during metaphase. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase activity. Important for microtubule formation and/or stabilization. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and destabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Inhibits cilia outgrowth (By similarity). Required for cilia disassembly via phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin. Regulates protein levels of the anti-apoptosis protein BIRC5 by suppressing the expression of the SCF(FBXL7) E3 ubiquitin-protein ligase substrate adapter FBXL7 through the phosphorylation of the transcription factor FOXP1.

References:

[1]. Doris Kinzel, et al. Pitchfork regulates primary cilia disassembly and left-right asymmetry. Dev Cell. 2010 Jul 20;19(1):66-77. [Content Brief]

[2]. Shingo Toji, et al. The centrosomal protein Lats2 is a phosphorylation target of Aurora-A kinase. Genes Cells. 2004 May;9(5):383-97. [Content Brief]

[3]. Libor Macůrek, et al. Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery. Nature. 2008 Sep 4;455(7209):119-23. [Content Brief]

[4]. Elena N Pugacheva, et al. HEF1-dependent Aurora A activation induces disassembly of the primary cilium. Cell. 2007 Jun 29;129(7):1351-63. [Content Brief]

[5]. Tomotoshi Marumoto, et al. Roles of aurora-A kinase in mitotic entry and G2 checkpoint in mammalian cells. Genes Cells. 2002 Nov;7(11):1173-82. [Content Brief]

[6]. Sachin Kotak, et al. Aurora A kinase regulates proper spindle positioning in C. elegans and in human cells. J Cell Sci. 2016 Aug 1;129(15):3015-25. [Content Brief]

[7]. A O Walter, et al. The mitotic serine/threonine kinase Aurora2/AIK is regulated by phosphorylation and degradation. Oncogene. 2000 Oct 5;19(42):4906-16. [Content Brief]

[8]. Hiroshi Katayama, et al. Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat Genet. 2004 Jan;36(1):55-62. [Content Brief]

[9]. Tomotoshi Marumoto, et al. Aurora-A kinase maintains the fidelity of early and late mitotic events in HeLa cells. J Biol Chem. 2003 Dec 19;278(51):51786-95. [Content Brief]

[10]. Chang-Young Jang, et al. Plk1 and Aurora A regulate the depolymerase activity and the cellular localization of Kif2a. J Cell Sci. 2009 May 1;122(Pt 9):1334-41. [Content Brief]

[11]. Sara Carvalhal, et al. The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation. Mol Biol Cell. 2015 Oct 1;26(19):3424-38. [Content Brief]

[12]. Stéphanie Dutertre, et al. Phosphorylation of CDC25B by Aurora-A at the centrosome contributes to the G2-M transition. J Cell Sci. 2004 May 15;117(Pt 12):2523-31. [Content Brief]

[13]. Toru Hirota, et al. Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells. Cell. 2003 Sep 5;114(5):585-98. [Content Brief]

[14]. M Kamran, et al. Aurora kinase A regulates Survivin stability through targeting FBXL7 in gastric cancer drug resistance and prognosis. Oncogenesis. 2017 Feb 20;6(2):e298. [Content Brief]

[15]. Mark G Manfredi, et al. Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase. Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4106-11. [Content Brief]

[16]. Daisuke Mori, et al. An essential role of the aPKC-Aurora A-NDEL1 pathway in neurite elongation by modulation of microtubule dynamics. Nat Cell Biol. 2009 Sep;11(9):1057-68. [Content Brief]

[17]. Chang-Tze Ricky Yu, et al. Phosphorylation and stabilization of HURP by Aurora-A: implication of HURP as a transforming target of Aurora-A. Mol Cell Biol. 2005 Jul;25(14):5789-800. [Content Brief]

[18]. Satish Sankaran, et al. Aurora-A kinase regulates breast cancer associated gene 1 inhibition of centrosome-dependent microtubule nucleation. Cancer Res. 2007 Dec 1;67(23):11186-94. [Content Brief]

[19]. H Katayama, et al. Interaction and feedback regulation between STK15/BTAK/Aurora-A kinase and protein phosphatase 1 through mitotic cell division cycle. J Biol Chem. 2001 Dec 7;276(49):46219-24. [Content Brief]

[20]. Daniele Fancelli, et al. 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: identification of a potent Aurora kinase inhibitor with a favorable antitumor kinase inhibition profile. J Med Chem. 2006 Nov 30;49(24):7247-51. [Content Brief]

[21]. Mohammad R Khazaei, et al. Phosphorylation of the par polarity complex protein Par3 at serine 962 is mediated by aurora a and regulates its function in neuronal polarity. J Biol Chem. 2009 Nov 27;284(48):33571-9. [Content Brief]

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