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Chemical Compound Review

Spotlight     ethyl 2-chloro-3-[2-chloro-5-[4...

Synonyms: Aurora, Kuaimieling, Spotlight 24EC, Aurora 50WG, HSDB 7253, ...
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Disease relevance of Spotlight

  • Our findings support a functional relationship between Aurora kinase expression and prostate cancer and the application of small-molecule inhibitors in therapeutic modalities [1].
  • A role for Aurora kinases in the aggressive behavior of mesotheliomas is of potential clinical interest because of the recent development of small-molecule inhibitors [2].
  • This reinforces the concept of preferential dysregulation of the centrosome complex in CIN-type (aneuploid), compared with MIN-type, sporadic colorectal cancers and may influence the response to and efficiency of novel therapeutics targeting Aurora kinases [3].
  • The block of Aurora B expression induced by RNA interference or by using an inhibitor of Aurora kinase activity significantly reduced the growth of thyroid anaplastic carcinoma cells [4].
  • The expression at the protein level of all 3 Aurora kinases was significantly higher in 3 thyroid papillary carcinomas with respect to normal matched tissues obtained from the same patients [5].
  • Aurora A and B expression was variable in primary breast tumors [6].

High impact information on Spotlight


Chemical compound and disease context of Spotlight


Biological context of Spotlight

  • Here we report the discovery of a highly potent and selective small-molecule inhibitor of Aurora kinases, VX-680, that blocks cell-cycle progression and induces apoptosis in a diverse range of human tumor types [10].
  • Recent work on both kinases has revealed functional links between Aurora kinase activity and the mechanics of cell division [12].
  • Here, we show that insulin also stimulates Aurora A-catalyzed CPEB S174 phosphorylation, cytoplasmic polyadenylation, translation, and oocyte maturation [13].
  • Why do polyploid cells containing abnormal centrosome numbers induced by Aurora not get eliminated at cell-cycle checkpoints [14]?
  • Here we show that by removal of small-molecule inhibitors, controlled activation of Aurora kinase during mitosis can correct chromosome attachment errors by selective disassembly of kinetochore-microtubule fibres, rather than by alternative mechanisms involving initial release of microtubules from either kinetochores or spindle poles [15].

Anatomical context of Spotlight


Associations of Spotlight with other chemical compounds


Gene context of Spotlight

  • Genetic, biochemical, and microarray analyses suggest that APC-dependent cell cycle control of H3 phosphorylation is exerted at the level of an Aurora H3 kinase, Ipl1p, while APC-dependent transcriptional induction of GLC7, an essential H3 phosphatase, contributes to sustained H3 dephosphorylation upon cell cycle withdrawal [23].
  • We have performed a detailed domain functional analysis of TPX2 and found that a large N-terminal domain containing the Aurora A binding peptide interacts directly with and nucleates microtubules in pure tubulin solutions [24].
  • Moreover, Mob1p, but not Cdc15p, is required for dissociating Aurora from the kinetochore region [25].
  • The recent determination of the three-dimensional structure of Aurora A has shown that Aurora kinases exhibit unique conformations around the activation loop region [26].
  • The function of Aurora-C kinase, a member of the Aurora kinase family identified in mammals, is currently unknown [27].
  • We report that heterologous expression of wild-type and kinase-inactive forms of TLK-1 suppresses the lethality of temperature-sensitive mutants of the yeast Aurora B kinase Ipl1 [28].

Analytical, diagnostic and therapeutic context of Spotlight

  • The microinjection of Inh-2 restores Aurora activation, CPEB hyperphosphorylation and cyclin B translation in enucleated oocytes [29].
  • Technological analysis of lithic artefacts recovered at the Aurora stratum of Atapuerca-TD6 shows that this Lower Pleistocene assemblage is similar to Mode I Technology (=Oldowan tradition) documented at many African sites [30].
  • By RT-PCR analysis in various tissues, Aurora C-SV, like Aurora C, was found to be expressed at the highest level in human testis [31].
  • The Aurora is a flexible platform that provides the desired renal therapy with ease of use and proper support for the hemodialysis patient when combined with Baxter's 24-hour infrastructure and support [32].
  • The Aurora encoding protein was detected in COS-7 transfected with different Aurora transcripts by Western blot [33].


  1. Targeting Aurora kinases for the treatment of prostate cancer. Lee, E.C., Frolov, A., Li, R., Ayala, G., Greenberg, N.M. Cancer Res. (2006) [Pubmed]
  2. Global gene expression profiling of pleural mesotheliomas: overexpression of aurora kinases and P16/CDKN2A deletion as prognostic factors and critical evaluation of microarray-based prognostic prediction. López-Ríos, F., Chuai, S., Flores, R., Shimizu, S., Ohno, T., Wakahara, K., Illei, P.B., Hussain, S., Krug, L., Zakowski, M.F., Rusch, V., Olshen, A.B., Ladanyi, M. Cancer Res. (2006) [Pubmed]
  3. Centrosome-, chromosomal-passenger- and cell-cycle-associated mRNAs are differentially regulated in the development of sporadic colorectal cancer. Gerlach, U., Kayser, G., Walch, A., Hopt, U., Schulte-Mönting, J., Werner, M., Lassmann, S. J. Pathol. (2006) [Pubmed]
  4. Aurora B overexpression associates with the thyroid carcinoma undifferentiated phenotype and is required for thyroid carcinoma cell proliferation. Sorrentino, R., Libertini, S., Pallante, P.L., Troncone, G., Palombini, L., Bavetsias, V., Spalletti-Cernia, D., Laccetti, P., Linardopoulos, S., Chieffi, P., Fusco, A., Portella, G. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  5. Expression of Aurora kinases in human thyroid carcinoma cell lines and tissues. Ulisse, S., Delcros, J.G., Baldini, E., Toller, M., Curcio, F., Giacomelli, L., Prigent, C., Ambesi-Impiombato, F.S., D'Armiento, M., Arlot-Bonnemains, Y. Int. J. Cancer (2006) [Pubmed]
  6. Expression of Aurora A (but not Aurora B) is predictive of survival in breast cancer. Nadler, Y., Camp, R.L., Schwartz, C., Rimm, D.L., Kluger, H.M., Kluger, Y. Clin. Cancer Res. (2008) [Pubmed]
  7. The NoCut pathway links completion of cytokinesis to spindle midzone function to prevent chromosome breakage. Norden, C., Mendoza, M., Dobbelaere, J., Kotwaliwale, C.V., Biggins, S., Barral, Y. Cell (2006) [Pubmed]
  8. Evidence that the Ipl1-Sli15 (Aurora kinase-INCENP) complex promotes chromosome bi-orientation by altering kinetochore-spindle pole connections. Tanaka, T.U., Rachidi, N., Janke, C., Pereira, G., Galova, M., Schiebel, E., Stark, M.J., Nasmyth, K. Cell (2002) [Pubmed]
  9. Translational control of the embryonic cell cycle. Groisman, I., Jung, M.Y., Sarkissian, M., Cao, Q., Richter, J.D. Cell (2002) [Pubmed]
  10. VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Harrington, E.A., Bebbington, D., Moore, J., Rasmussen, R.K., Ajose-Adeogun, A.O., Nakayama, T., Graham, J.A., Demur, C., Hercend, T., Diu-Hercend, A., Su, M., Golec, J.M., Miller, K.M. Nat. Med. (2004) [Pubmed]
  11. Clinical development of levetiracetam for amyotrophic lateral sclerosis. Davies, S.L., Moral, M.A. Drug News Perspect. (2006) [Pubmed]
  12. Mitotic mechanics: the auroras come into view. Andrews, P.D., Knatko, E., Moore, W.J., Swedlow, J.R. Curr. Opin. Cell Biol. (2003) [Pubmed]
  13. Progesterone and insulin stimulation of CPEB-dependent polyadenylation is regulated by Aurora A and glycogen synthase kinase-3. Sarkissian, M., Mendez, R., Richter, J.D. Genes Dev. (2004) [Pubmed]
  14. Aurora kinases, aneuploidy and cancer, a coincidence or a real link? Giet, R., Petretti, C., Prigent, C. Trends Cell Biol. (2005) [Pubmed]
  15. Correcting improper chromosome-spindle attachments during cell division. Lampson, M.A., Renduchitala, K., Khodjakov, A., Kapoor, T.M. Nat. Cell Biol. (2004) [Pubmed]
  16. Regulation of Xenopus Aurora A activation by TPX2. Eyers, P.A., Maller, J.L. J. Biol. Chem. (2004) [Pubmed]
  17. Inhibition of Aurora kinases perturbs chromosome alignment and spindle checkpoint signaling in rat spermatocytes. Wang, Y., Toppari, J., Parvinen, M., Kallio, M.J. Exp. Cell Res. (2006) [Pubmed]
  18. Gene expression profiles of the aurora family kinases. Lin, Y.S., Su, L.J., Yu, C.T., Wong, F.H., Yeh, H.H., Chen, S.L., Wu, J.C., Lin, W.J., Shiue, Y.L., Liu, H.S., Hsu, S.L., Lai, J.M., Huang, C.Y. Gene Expr. (2006) [Pubmed]
  19. Downregulation of an AIM-1 kinase couples with megakaryocytic polyploidization of human hematopoietic cells. Kawasaki, A., Matsumura, I., Miyagawa Ji, n.u.l.l., Ezoe, S., Tanaka, H., Terada, Y., Tatsuka, M., Machii, T., Miyazaki, H., Furukawa, Y., Kanakura, Y. J. Cell Biol. (2001) [Pubmed]
  20. Activation of Aurora-A kinase by protein phosphatase inhibitor-2, a bifunctional signaling protein. Satinover, D.L., Leach, C.A., Stukenberg, P.T., Brautigan, D.L. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  21. The in vitro and in vivo effects of JNJ-7706621: a dual inhibitor of cyclin-dependent kinases and aurora kinases. Emanuel, S., Rugg, C.A., Gruninger, R.H., Lin, R., Fuentes-Pesquera, A., Connolly, P.J., Wetter, S.K., Hollister, B., Kruger, W.W., Napier, C., Jolliffe, L., Middleton, S.A. Cancer Res. (2005) [Pubmed]
  22. Localization of human TACC3 to mitotic spindles is mediated by phosphorylation on Ser558 by Aurora A: a novel pharmacodynamic method for measuring Aurora A activity. LeRoy, P.J., Hunter, J.J., Hoar, K.M., Burke, K.E., Shinde, V., Ruan, J., Bowman, D., Galvin, K., Ecsedy, J.A. Cancer Res. (2007) [Pubmed]
  23. Global control of histone modification by the anaphase-promoting complex. Ramaswamy, V., Williams, J.S., Robinson, K.M., Sopko, R.L., Schultz, M.C. Mol. Cell. Biol. (2003) [Pubmed]
  24. Characterization of the TPX2 domains involved in microtubule nucleation and spindle assembly in Xenopus egg extracts. Brunet, S., Sardon, T., Zimmerman, T., Wittmann, T., Pepperkok, R., Karsenti, E., Vernos, I. Mol. Biol. Cell (2004) [Pubmed]
  25. The mitotic exit network Mob1p-Dbf2p kinase complex localizes to the nucleus and regulates passenger protein localization. Stoepel, J., Ottey, M.A., Kurischko, C., Hieter, P., Luca, F.C. Mol. Biol. Cell (2005) [Pubmed]
  26. Aurora kinases. Bolanos-Garcia, V.M. Int. J. Biochem. Cell Biol. (2005) [Pubmed]
  27. Aurora-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells. Sasai, K., Katayama, H., Stenoien, D.L., Fujii, S., Honda, R., Kimura, M., Okano, Y., Tatsuka, M., Suzuki, F., Nigg, E.A., Earnshaw, W.C., Brinkley, W.R., Sen, S. Cell Motil. Cytoskeleton (2004) [Pubmed]
  28. Tousled-mediated activation of Aurora B kinase does not require Tousled kinase activity in vivo. Riefler, G.M., Dent, S.Y., Schumacher, J.M. J. Biol. Chem. (2008) [Pubmed]
  29. Nuclear envelope breakdown may deliver an inhibitor of protein phosphatase 1 which triggers cyclin B translation in starfish oocytes. Lapasset, L., Pradet-Balade, B., Lozano, J.C., Peaucellier, G., Picard, A. Dev. Biol. (2005) [Pubmed]
  30. The TD6 level lithic industry from Gran Dolina, Atapuerca (Burgos, Spain): production and use. Carbonell, E., García-Antón, M.D., Mallol, C., Mosquera, M., Ollé, A., Rodríguez, X.P., Sahnouni, M., Sala, R., Vergès, J.M. J. Hum. Evol. (1999) [Pubmed]
  31. Cloning and characterization of a novel human Aurora C splicing variant. Yan, X., Wu, Y., Li, Q., Cao, L., Liu, X., Saiyin, H., Yu, L. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  32. Baxter Aurora dialysis system. Kelly, T.D. Seminars in dialysis. (2004) [Pubmed]
  33. Expression of Aurora-B kinase and phosphorylated histone H3 in hepatocellular carcinoma. Sistayanarain, A., Tsuneyama, K., Zheng, H., Takahashi, H., Nomoto, K., Cheng, C., Murai, Y., Tanaka, A., Takano, Y. Anticancer Res. (2006) [Pubmed]
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