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Aurora Kinases : the Secret of Mitotic Regulation

            Mammals have three aurora kinases: Aurora A, Aurora B and Aurora C. The Aurora kinases are related to the AGC branch of protein kinases (protein kinase A, protein kinase G, protein kinase C). Part of the activation mechanism for most AGC kinases is binding of a C-terminal “hydrophobic motif”, FXXF(T/S)F, to the N-terminal lobe of the kinase. This binding often requires phosphorylation of a serine or threonine residue in the hydrophobic motif. However Aurora kinases, instead of binding to such a hydrophobic motif in their C-terminus, bind other proteins to their N-terminal lobe. One such co-factor for Aurora A is the protein TPX2. For Aurora B and C the C-terminal section of the INCENP protein performs a similar function. For part of the cell cycle Aurora B exists as a part of the larger Chromosomal Passenger Complex (CPC) consisting of Aurora B, INCENP, Survivin and Borealin. This complex is required for proper localisation of Aurora B during mitosis.

           Due to their role in mitotic regulation, the Aurora kinases are seen as targets for inhibition for treatment of cancers, and many Aurora inhibitors have been developed, including some isoform-specific inhibitors.

          The structure of Aurora B has previously been determined from Xenopus laevis, in complex with the Aurora B inhibitor Hesperadin. In the photo presented here, it ishows the structure of human Aurora B kinase in complex with the C-terminal section of INCENP and the pan-Aurora inhibitor VX-680.

(Source: Elkins et al., 2012. The Structural Genomics Consortium. )