Aurora A kinase

Centromere protein A (CENP-A), one of several variants of histone H3, is phosphorylated on Ser 7 by Aurora B kinase which is equivalent to Ser 10 of histone H3 (Zeitlin et al, 2001). Recent studies demonstrate that Aurora A kinase also phosphorylates CENP-A (S7) (Kunitoku et al, 2003) (Table 1). The presence of CENP-A in centromeric nucleosomes is required for kinetochore organization and function (Choo 2001). Loss of CENP-A phosphorylation function at Ser 7 caused a mislocalisation of Aurora B, a putative partner phosphatase (PPl-yl) and inner centromere protein (INCENP). H3.3, another variant of histone H3 is phosphorylated on Ser 31 in vivo (Table 1). H3.3 (S31) is a mitosis-specific modification that is present only in late prometaphase and metaphase. Furthermore, H3.3 (S31) is excluded from centromeres. However it is enriched in distinct chromosomal areas immediately adjacent to centromeres (Hake et al, 2005). 

Scrittori L, Hans F, Angelov D, Charra M, Prigent C, Dimitrov S (2001) pEg2 aurora-A kinase, histone H3 phosphorylation, and chromosome assembly in Xenopus egg extract. J Biol Chem 276(32) 30002-30010... 

Anaphase TPX2 Localization of Aurora A kinase to mitotic spindles 353... 

Very recently Erlanson and colleagues described the discovery of aurora A kinase inhibitors using a purely dynamic chemistry approach [27] that... 

Pfizer (Pharmacia) disclosed the development of potent Aurora-A kinase inhibitors containing the 3-aminothieno[3,2-c]pyrazole (80) and 3-amino-furo[3,2-c]pyrazole (81) scaffolds [195,196]. Extensive data was not reported... 

Activation of Aurora-A kinase by protein phosphatase inhibitor-2, a bifimctional signaling protein. Proc Natl Acad Sci USA 101 8625-8630... 

Michael condensation of 1 and frans-/)-benzoylacrylic acid afforded butanoic acid derivative 315 that can be cyclized, with ammonia in an autoclave at 150-160 °C, to give 7,7-dimethyl-4-phenyl-l,2,6,7,8,8a-hexahydro-pyrrolo[4,3,2-d,e]quinolin-2-one (316) (97JOU1048). The pyr-rolo[3,4-fr]quinoline 317 was reported as inhibitor of Aurora A Kinase (07EUP60) (Scheme 59). 

Marumoto, T., Hirota, T., Morisaki, T., Kunitoku, N., Zhang, D., Ichikawa, Y., et al. (2002). Roles of aurora-A kinase in mitotic entry and G2 checkpoint in mammalian cells. Genes to Cells Devoted to Molecular Cellular Mechanisms, 7, 1173-1182. 

Ma C, Cummings C, Liu XJ. 2003. Biphasic activation of Aurora-A kinase during the meiosis I- meiosis II transition in Xenopus oocytes. Mol Cell Biol 23(5) 1703-1716. 

Pascreau G, Delcros JG, Morin N, Prigent C, Arlot-Bonnemains Y. 2008. Aurora-A kinase Ser349 phosphorylation is required during Xenopus laevis oocyte maturation. Dev Biol 317(2) 523-530. 

Petit J, Meurice N, Mousses S, et al. Applications of rough sets theory in drug discovery Analysis of HTS data relative to the inhibition of Aurora A kinase. 236th National American Chemical Society Meeting 2008 Aug 17-21 Philadelphia. Division of Chemical Information Abstr. No. 40. 

Figure 1.2 Structures of some inhibitors of Aurora A kinase (22) and p38 MAP kinase (23) discovered using a DNA-encoded small-molecule library.

Aurora-A Kinase CeU division (important for progression of G2/M phase) Formation of AUKAIP1 -AZ 1 -Aurora-A ternary complex In vivo Lim and Gopalan (2007)... 

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