Aurora kinase

Aurora protein kinase (Aurora A/B/C/AIR-2/Eg2/IAK2/lpl1p)... 

Littlepage LE, Ruderman JV. 2002. Identification of a new APC/C recognition domain, the A box, which is required for the Cdhl-dependent destruction of the kinase Aurora-A during mitotic exit. Genes Dev 16(17) 2274-2285. 

Identification of phosphoiylated residues that affect the activity of the mitotic kinase Aurora-A. Proc Natl Acad Sci USA 99(24) 15440-15445. 

Huang, Y. S., Jung, M. Y., Sarkissian, M., and Richter, J. D. (2002). N-methyl-D-aspartate receptor signaling results in Aurora kinase-catalyzed CPEB phosphorylation and alpha CaMKII mRNA polyadenylation at synapses. EMBOJ. 21, 2139-2148. 

Phosphorylation has been thought to be correlated to the mitotic chromatin condensation and the transcriptional regulation in interphase (Nowak and Corces, 2004). The mitotic phosphorylation, which was first identified in 1978 (Gurley et al, 1978), occurs at Ser (Wei et al, 1998), Ser (Goto et al, 1999), and Thr (Preuss et al, 2003) in histone H3. The Ser phosphorylation is catalyzed by the aurora kinase family (de la Barre et al, 2000), and is required for the initiation of chromosome condensation but not for its maintenance (dephosphorylation of mitotic chromosomes does not induce chromosome decondensation) (Van Hooser et fl/.,1998). In meiosis, Ser phosphorylation is also required for the cohesion of sister chromatids rather than the condensation (Kaszas and Cande, 2000). 

Histone H3 (Til) phosphorylation occurs during mitosis by Dlk/ZIP kinase (Dlk Death-associated protein (DAP)-like kinase, ZIP Zipper interacting protein kinase) (Preuss et al, 2003) (Table 1). Histone H3 at Serine 28 is phosphorylated by Aurora B kinase at mitosis and this phosphorylation coincides with chromosome condensation (Goto et al., 1999, Goto et al, 2002) (Fig. 2), (Table 1). Histone H3 (S28) phosphorylation initiates at prophase, whereas histone H3 (SIO) phosphorylation initiates during the late G2 phase (Hendzel et al, 1997). 

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). 

Adams RR, Maiato H, Earnshaw WC, Carmena M (2001) Essential roles of Drosophila inner centromere protein (INCENP) and aurora B in histone H3 phosphorylation, metaphase chromosome ahgnment, kinetochore disjunction, chromosome segregation. J Cell Biol 153(4) 865-880 Ahn SH, Cheung WL, Hsu JY, Diaz RL, Smith MM, Alhs CD (2005a) Sterile 20 kinase phospho-rylates histone H2B at serine 10 during hydrogen peroxide-induced apoptosis in S. cerevisiae. Cell 120(l) 25-36... 

Contreras A, Hale TK, Stenoien DL, Rosen JM, Mancini MA, Herrera RE (2003) The dynamic mobility of histone HI is regulated by cyclin/CDK phosphorylation. Mol Cell Biol 23(23) 8626-8636 Crosio C, Fimia GM, Loury R, Kimura M, Okano Y, Zhou H, Sen S, Allis CD, Sassone-Corsi P (2002) Mitotic phosphorylation of histone H3 spatio-temporal regulation by mammalian Aurora kinases. Mol Cell Biol 22(3) 874-885... 

Ge Z, Liu C, Bjorkholm M, Gruber A, Xu D (2006) Mitogen-activated protein kinase cascade-mediated histone H3 phosphorylation is critical for telomerase reverse transcriptase expression/telomerase activation induced by proliferation. Mol Cell Biol 26(l) 230-237 Giet R, Glover DM (2001) Drosophila aurora B kinase is required for histone H3 phosphorylation and condensin recruitment during chromosome condensation and to organize the central spindle during cytokinesis. J Cell Biol 152(4) 669-682... 

Ota T, Suto S, Katayama H, Han ZB, Suzuki F, Maeda M, Tanino M, Terada Y, Tatsuka M (2002) Increased mitotic phosphorylation of histone H3 attributable to AIM-l/Aurora-B overexpression contributes to chromosome number instability. Cancer Res 62(18) 5168-5177 Paulson JR, Taylor SS (1982) Phosphorylation of histones 1 and 3 and nonhistone high mobihty group 14 by an endogenous kinase in HeLa metaphase chromosomes. J Biol Chem 257(11) 6064—6072 Petersen J, Paris J, Wilier M, Philippe M, Hagan IM (2001) The S. pombe aurora-related kinase Arkl associates with mitotic structures in a stage dependent manner and is required for chromosome segregation. J Cell Sci 114(Pt 24) 4371 384... 

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... 

Sugiyama K, Sugiura K, Kara T, Sugimoto K, Shima H, Honda K, Furukawa K, Yamashita S, Urano T (2002) Aurora-B associated protein phosphatases as negative regulators of kinase activation. Oncogene... 

ZeitUn SG, Shelby RD, Sullivan KF (2001) CENP-A is phosphorylated by Aurora B kinase and plays an unexpected role in completion of cytokinesis. J Cell Biol 155(7) 1147-1157 Zhang Y, Griffin K, Mondal N, Parvin JD (2004) Phosphorylation of histone H2A inhibits transcription on chromatin templates. J Biol Chem 279(21) 21866-21872... 

The phenylselenocysteine has also been used successfully to chemically append analogues of methyl- or acetyl-lysine, important histone modifications that can contribute to chromatin structure and accessibility of transcriptional machinery in eukaryotes. By introducing phenylselenocysteine into the Xenopus histone H3, both acetyl-lysine and mono-, di-, and trimethyl-lysine analogues were appended to the purified unnatural amino acid-containing FI 3 protein (Figure 10). " Additionally, the H3 protein with a modification mimicking acetylation of lysine 9 can be deactylated by a histone deacetylation complex and is also a substrate for phosphorylation by Aurora B kinase. Such purified and chemically labeled histones are likely functional in nucleosomes, and preparation of specifically modified histones for comprehensive analysis of chromatin structure and accessibility is particularly suited to this chemical labeling technique. 

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

In vitro studies with unmodified and modified N-terminal peptides of H3 demonstrated that Lys-14 acetylation did not interfere with methylation at Lys-9 by Suv39hl, while phosphorylation at Ser-10 and acetylation at Lys-9 did (Fig. 7). Further dimethylation of Lys-9 reduced enzymatic activity [186], A Suv39h double null primary mouse embryonic fibroblasts had higher levels of Ser-10 phos-phorylated H3 than wild type cells. These mutant cells had increased numbers of micro- and polynuclei. Oversized nuclei were characteristic of subpopulation of cells. The level of Lys-9 methylated FI3 in wild type cells and Suv39h double null cells was similar, demonstrating that other FI3 methyltransferases were involved [195]. Phosphorylation of Ser-10 by Ipll/aurora was also studied. Acetylation at Lys-14 promoted the activity of the mitotic kinase, while dimethylation, but not acetylation at Lys-9, reduced activity of the kinase [186]. 

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

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