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Aurka  -  aurora kinase A

Mus musculus

Synonyms: AIRK1, ARK-1, AU019385, AW539821, Aik, ...
 
 
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Disease relevance of Aurka

 

High impact information on Aurka

  • Chfr deficiency leads to chromosomal instability in embryonic fibroblasts and regulates the mitotic kinase Aurora A, which is frequently upregulated in a variety of tumors [6].
  • Collectively, our data suggest that Chfr is a tumor suppressor and ensures chromosomal stability by controlling the expression levels of key mitotic proteins such as Aurora A [6].
  • Identification of a new APC/C recognition domain, the A box, which is required for the Cdh1-dependent destruction of the kinase Aurora-A during mitotic exit [7].
  • The mitotic kinase Aurora A (Aur-A) is required for formation of a bipolar mitotic spindle and accurate chromosome segregation [7].
  • PAK1 promotes phosphorylation of Aurora-A on Thr288 and Ser342, which are key sites for kinase activation in mitosis [8].
 

Chemical compound and disease context of Aurka

  • Treatment of animals carrying tumor IAK 109D with 3,5,3'-triiodo-L-thyronine (T3) (5 micrograms/100 g body weight) for 2 hr reduced TSH-beta gene transcription to less than 10% of control levels, whereas alpha RNA synthesis was reduced to 59% of control [9].
 

Biological context of Aurka

 

Anatomical context of Aurka

  • Under the exponential growth conditions of MEF cells, transgenic Aurora A was detected within the mitotic stage of the cell cycle and localized to centrosomes [10].
  • Cell lines and primary tumors derived from the TRAMP model were also found to express high levels of Aurora-A and Aurora-B [2].
  • Interestingly, expression of Aurora-A in non-neoplastic prostates correlated with seminal vesicle invasion (rho = 0.275, P = 0.0169) and in prostate tumor with positive surgical margins (rho = 0.265, P = 0.0161) [2].
  • Here, we created a transgenic mouse model to investigate the involvement of Aurora-A overexpression in the development of mammary glands and tumorigenesis using a Cre-loxP system [3].
  • The quantity of aurora-A protein was high in the germinal vesicle (GV) and metaphase II (MII) oocytes and remained stable during other meiotic maturation stages [12].
 

Associations of Aurka with chemical compounds

 

Other interactions of Aurka

  • 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 [17].
  • In vitro studies using mouse embryo fibroblasts demonstrate that inhibition of Aurora-A can have either positive or negative effects on cell growth as a function of p53 status [18].
 

Analytical, diagnostic and therapeutic context of Aurka

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. Cre-loxP-controlled periodic Aurora-A overexpression induces mitotic abnormalities and hyperplasia in mammary glands of mouse models. Zhang, D., Hirota, T., Marumoto, T., Shimizu, M., Kunitoku, N., Sasayama, T., Arima, Y., Feng, L., Suzuki, M., Takeya, M., Saya, H. Oncogene (2004) [Pubmed]
  4. BRCA1 phosphorylation by Aurora-A in the regulation of G2 to M transition. Ouchi, M., Fujiuchi, N., Sasai, K., Katayama, H., Minamishima, Y.A., Ongusaha, P.P., Deng, C., Sen, S., Lee, S.W., Ouchi, T. J. Biol. Chem. (2004) [Pubmed]
  5. Identification of Aurora-A as a direct target of E2F3 during G2/M cell cycle progression. He, L., Yang, H., Ma, Y., Pledger, W.J., Cress, W.D., Cheng, J.Q. J. Biol. Chem. (2008) [Pubmed]
  6. Chfr is required for tumor suppression and Aurora A regulation. Yu, X., Minter-Dykhouse, K., Malureanu, L., Zhao, W.M., Zhang, D., Merkle, C.J., Ward, I.M., Saya, H., Fang, G., van Deursen, J., Chen, J. Nat. Genet. (2005) [Pubmed]
  7. Identification of a new APC/C recognition domain, the A box, which is required for the Cdh1-dependent destruction of the kinase Aurora-A during mitotic exit. Littlepage, L.E., Ruderman, J.V. Genes Dev. (2002) [Pubmed]
  8. The GIT-associated kinase PAK targets to the centrosome and regulates Aurora-A. Zhao, Z.S., Lim, J.P., Ng, Y.W., Lim, L., Manser, E. Mol. Cell (2005) [Pubmed]
  9. Thyroid hormone regulation of thyrotropin alpha- and beta-subunit gene transcription. Gurr, J.A., Kourides, I.A. DNA (1985) [Pubmed]
  10. Conditional transgenic system for mouse aurora a kinase: degradation by the ubiquitin proteasome pathway controls the level of the transgenic protein. Fukuda, T., Mishina, Y., Walker, M.P., DiAugustine, R.P. Mol. Cell. Biol. (2005) [Pubmed]
  11. Caenorhabditis elegans Aurora A kinase AIR-1 is required for postembryonic cell divisions and germline development. Furuta, T., Baillie, D.L., Schumacher, J.M. Genesis (2002) [Pubmed]
  12. Aurora-A is a critical regulator of microtubule assembly and nuclear activity in mouse oocytes, fertilized eggs, and early embryos. Yao, L.J., Zhong, Z.S., Zhang, L.S., Chen, D.Y., Schatten, H., Sun, Q.Y. Biol. Reprod. (2004) [Pubmed]
  13. Amyloid precursor proteins anchor CPEB to membranes and promote polyadenylation-induced translation. Cao, Q., Huang, Y.S., Kan, M.C., Richter, J.D. Mol. Cell. Biol. (2005) [Pubmed]
  14. Two functional coding single nucleotide polymorphisms in STK15 (Aurora-A) coordinately increase esophageal cancer risk. Kimura, M.T., Mori, T., Conroy, J., Nowak, N.J., Satomi, S., Tamai, K., Nagase, H. Cancer Res. (2005) [Pubmed]
  15. Regulation of Aurora-A kinase gene expression via GABP recruitment of TRAP220/MED1. Udayakumar, T.S., Belakavadi, M., Choi, K.H., Pandey, P.K., Fondell, J.D. J. Biol. Chem. (2006) [Pubmed]
  16. Discovery of novel and potent thiazoloquinazolines as selective Aurora A and B kinase inhibitors. Jung, F.H., Pasquet, G., Lambert-van der Brempt, C., Lohmann, J.J., Warin, N., Renaud, F., Germain, H., De Savi, C., Roberts, N., Johnson, T., Dousson, C., Hill, G.B., Mortlock, A.A., Heron, N., Wilkinson, R.W., Wedge, S.R., Heaton, S.P., Odedra, R., Keen, N.J., Green, S., Brown, E., Thompson, K., Brightwell, S. J. Med. Chem. (2006) [Pubmed]
  17. 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]
  18. Crosstalk between Aurora-A and p53: frequent deletion or downregulation of Aurora-A in tumors from p53 null mice. Mao, J.H., Wu, D., Perez-Losada, J., Jiang, T., Li, Q., Neve, R.M., Gray, J.W., Cai, W.W., Balmain, A. Cancer. Cell (2007) [Pubmed]
  19. Frequent overexpression of STK15/Aurora-A/BTAK and chromosomal instability in tumorigenic cell cultures derived from human ovarian cancer. Hu, W., Kavanagh, J.J., Deaver, M., Johnston, D.A., Freedman, R.S., Verschraegen, C.F., Sen, S. Oncol. Res. (2005) [Pubmed]
 
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