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Aurkc  -  aurora kinase C

Mus musculus

Synonyms: AIE1, AIK3, ARK-3, Aie1, Aik3, ...
 
 
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Disease relevance of Aurkc

  • Overexpression of Aurora-A readily transforms rat-1 and NIH3T3 cells, but not primary cells, whereas overexpression of Aurora-B induces metastasis after implantation of tumors in nude mice [1].
  • In addition, nuclear expression of Aurora-B in prostatic intraepithelial neoplasia lesions correlated with clinical staging of the tumor (rho = -0.4, P = 0.0474) whereas cytoplasmic expression in tumors correlated with seminal vesicle invasion (rho = 0.282, P = 0.0098) [2].
  • Here, we report that Aurora-A and Aurora-B are highly expressed in primary human and mouse prostate cancers and prostate cancer cell lines [2].
  • Levels of Aurora-B are increased in several human cancers, and we show here that HsINCENP protein levels are also significantly increased in several colorectal cancer cell lines [3].
  • Here, we found that survivin, a member of the apoptosis-inhibiting gene family, and aurora B kinase, a chromosomal passenger protein, were co-overexpressed in the various glioblastoma cell lines and tumors [4].
 

High impact information on Aurkc

  • The cell cycle-regulated Aurora-B kinase is a chromosomal passenger protein that is implicated in fundamental mitotic events, including chromosome alignment and segregation and spindle checkpoint function [5].
  • Aurora-B becomes highly poly(ADP-ribosyl)ated in response to DNA damage, a modification that leads to a striking inhibition of its kinase activity [5].
  • Aurora-B phosphorylates serine 10 of histone H3, a function that has been associated with mitotic chromatin condensation [5].
  • In addition, we confirmed our earlier report on effects of constitutive expression of Aurora-B, indicating a tight regulation at protein level and a modest effect on MK ploidy [6].
  • Megakaryocytes express functional Aurora-B kinase in endomitosis [7].
 

Biological context of Aurkc

  • Aurora-B first appears at chromocentres in late diplotene before the initial phosphorylation of histone H3 [8].
  • INCENP and aurora-B kinase are two chromosomal passenger proteins that are thought to play key roles in coordinating chromosome segregation with cytokinesis in somatic cells [8].
  • Dynamic relocalization of the chromosomal passenger complex proteins inner centromere protein (INCENP) and aurora-B kinase during male mouse meiosis [8].
  • INCENP and aurora-B concentrate at centromeres during diakinesis and appear during metaphase I as T-shaped signals at their inner domains, just below associated sister kinetochores [8].
  • Aurora-B is an evolutionally conserved protein kinase that regulates several mitotic events including cytokinesis [9].
 

Anatomical context of Aurkc

 

Associations of Aurkc with chemical compounds

  • We previously reported two novel testis-specific serine/threonine kinases, Aie1 (mouse) and AIE2 (human), that share high amino acid identities with the kinase domains of fly aurora and yeast Ipl1 [11].
 

Enzymatic interactions of Aurkc

 

Regulatory relationships of Aurkc

 

Other interactions of Aurkc

  • The central kinase domain of AIE1 revealed 77.6% and 66.3% identity with that of STK-1 and IAK1/Ayk1, but much less homology was found in the sequence outside the kinase domain [13].
  • We further identified eight Aurora-B phosphorylation sites, including Ser-72 on vimentin, and then constructed the mutant vimentin in which these identified sites are changed into Ala [9].
  • Human INCENP colocalizes with the Aurora-B/AIRK2 kinase on chromosomes and is overexpressed in tumour cells [3].
 

Analytical, diagnostic and therapeutic context of Aurkc

References

  1. Aurora kinases, aneuploidy and cancer, a coincidence or a real link? Giet, R., Petretti, C., Prigent, C. Trends Cell Biol. (2005) [Pubmed]
  2. 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]
  3. Human INCENP colocalizes with the Aurora-B/AIRK2 kinase on chromosomes and is overexpressed in tumour cells. Adams, R.R., Eckley, D.M., Vagnarelli, P., Wheatley, S.P., Gerloff, D.L., Mackay, A.M., Svingen, P.A., Kaufmann, S.H., Earnshaw, W.C. Chromosoma (2001) [Pubmed]
  4. Survivin inhibits anti-growth effect of p53 activated by aurora B. Jung, J.E., Kim, T.K., Lee, J.S., Oh, S.Y., Kwak, S., Jin, X., Sohn, J.Y., Song, M.K., Sohn, Y.W., Lee, S.Y., Pian, X., Lee, J.B., Chung, Y.G., Choi, Y.K., You, S., Kim, H. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  5. Inhibition of Aurora-B kinase activity by poly(ADP-ribosyl)ation in response to DNA damage. Monaco, L., Kolthur-Seetharam, U., Loury, R., Murcia, J.M., de Murcia, G., Sassone-Corsi, P. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  6. Conditional overexpression of transgenes in megakaryocytes and platelets in vivo. Nguyen, H.G., Yu, G., Makitalo, M., Yang, D., Xie, H.X., Jones, M.R., Ravid, K. Blood (2005) [Pubmed]
  7. Megakaryocytes express functional Aurora-B kinase in endomitosis. Geddis, A.E., Kaushansky, K. Blood (2004) [Pubmed]
  8. Dynamic relocalization of the chromosomal passenger complex proteins inner centromere protein (INCENP) and aurora-B kinase during male mouse meiosis. Parra, M.T., Viera, A., Gómez, R., Page, J., Carmena, M., Earnshaw, W.C., Rufas, J.S., Suja, J.A. J. Cell. Sci. (2003) [Pubmed]
  9. Aurora-B regulates the cleavage furrow-specific vimentin phosphorylation in the cytokinetic process. Goto, H., Yasui, Y., Kawajiri, A., Nigg, E.A., Terada, Y., Tatsuka, M., Nagata, K., Inagaki, M. J. Biol. Chem. (2003) [Pubmed]
  10. The zinc finger domain of Tzfp binds to the tbs motif located at the upstream flanking region of the Aie1 (aurora-C) kinase gene. Tang, C.J., Chuang, C.K., Hu, H.M., Tang, T.K. J. Biol. Chem. (2001) [Pubmed]
  11. Genomic organization, expression, and chromosome localization of a third aurora-related kinase gene, Aie1. Hu, H.M., Chuang, C.K., Lee, M.J., Tseng, T.C., Tang, T.K. DNA Cell Biol. (2000) [Pubmed]
  12. Aberrant quantity and localization of Aurora-B/AIM-1 and survivin during megakaryocyte polyploidization and the consequences of Aurora-B/AIM-1-deregulated expression. Zhang, Y., Nagata, Y., Yu, G., Nguyen, H.G., Jones, M.R., Toselli, P., Jackson, C.W., Tatsuka, M., Todokoro, K., Ravid, K. Blood (2004) [Pubmed]
  13. Protein kinase profile of sperm and eggs: cloning and characterization of two novel testis-specific protein kinases (AIE1, AIE2) related to yeast and fly chromosome segregation regulators. Tseng, T.C., Chen, S.H., Hsu, Y.P., Tang, T.K. DNA Cell Biol. (1998) [Pubmed]
  14. Mutational analysis of the phosphorylation sites of the Aie1 (Aurora-C) kinase in vitro. Chen, S.H., Tang, T.K. DNA Cell Biol. (2002) [Pubmed]
 
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