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Gene Review

AURKA  -  aurora kinase A

Homo sapiens

Synonyms: AIK, AIRK1, ARK-1, ARK1, AURA, ...
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Disease relevance of AURKA


High impact information on AURKA


Chemical compound and disease context of AURKA


Biological context of AURKA

  • Thus our results support the importance of AURKA 91A as a low penetrance CRC susceptibility factor [2].
  • The degree of overexpression of AURKA was shown to be closely associated with the amplification of chromosome 20q in immortalized HOSE cells [12].
  • Quantitative expression analysis detected the overexpression of the AURKA gene in all tumors tested, suggesting a role for this mitotic regulator in the aneuploidy and chromosomal instability observed in RMS [13].
  • Aurora-A/BTAK/STK15 localizes to the centrosome in the G(2)-M phase, and its kinase activity regulates the G(2) to M transition of the cell cycle [14].
  • These results suggest the highly dynamic nature of the temporal and spatial distributions, as well as the biochemical modification, of the NuRD complex in M phase, probably through an interaction with kinases, including Aurora-A [15].

Anatomical context of AURKA


Associations of AURKA with chemical compounds


Physical interactions of AURKA

  • The centrosomal kinase Aurora-A/STK15 interacts with a putative tumor suppressor NM23-H1 [23].
  • Pull-down assays show that Plk3 physically interacts with Aurora A as well as BubR1 [19].
  • A two-hybrid screen identified the kinetochore component CENP-A as a protein that interacts with Aurora-A [24].
  • The E2 ubiquitin-conjugating enzyme UBE2N was a preferential binding partner of the 'weak' STK15 Phe31 variant form in yeast two-hybrid screens and in human cells [25].
  • Here we show that human Aurora-A binds to TPX2, a prominent component of the spindle apparatus [26].

Enzymatic interactions of AURKA

  • We have uncovered the molecular mechanism of Aurora-A activation by determining crystal structures of its phosphorylated form both with and without a 43 residue long domain of TPX2 that we identified as fully functional for kinase activation and protection from dephosphorylation [27].
  • Our results demonstrate that Aurora-A phosphorylates CDC25B in vivo at the centrosome during mitosis [28].
  • Moreover, Aurora-A phosphorylated HURP in vitro and in vivo [29].
  • Here, we show that Aurora-A phosphorylates NDEL1 at Ser251 at the beginning of mitotic entry [30].

Regulatory relationships of AURKA


Other interactions of AURKA


Analytical, diagnostic and therapeutic context of AURKA


  1. AURKA is one of the downstream targets of MAPK1/ERK2 in pancreatic cancer. Furukawa, T., Kanai, N., Shiwaku, H.O., Soga, N., Uehara, A., Horii, A. Oncogene (2006) [Pubmed]
  2. Preferential amplification of AURKA 91A (Ile31) in familial colorectal cancers. Hienonen, T., Salovaara, R., Mecklin, J.P., Järvinen, H., Karhu, A., Aaltonen, L.A. Int. J. Cancer (2006) [Pubmed]
  3. Overexpression of aurora B kinase (AURKB) in primary non-small cell lung carcinoma is frequent, generally driven from one allele, and correlates with the level of genetic instability. Smith, S.L., Bowers, N.L., Betticher, D.C., Gautschi, O., Ratschiller, D., Hoban, P.R., Booton, R., Santibáñez-Koref, M.F., Heighway, J. Br. J. Cancer (2005) [Pubmed]
  4. Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer. Li, D., Zhu, J., Firozi, P.F., Abbruzzese, J.L., Evans, D.B., Cleary, K., Friess, H., Sen, S. Clin. Cancer Res. (2003) [Pubmed]
  5. 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]
  6. Predictive value of Aurora-A/STK15 expression for late stage epithelial ovarian cancer patients treated by adjuvant chemotherapy. Lassmann, S., Shen, Y., Jütting, U., Wiehle, P., Walch, A., Gitsch, G., Hasenburg, A., Werner, M. Clin. Cancer Res. (2007) [Pubmed]
  7. Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Katayama, H., Sasai, K., Kawai, H., Yuan, Z.M., Bondaruk, J., Suzuki, F., Fujii, S., Arlinghaus, R.B., Czerniak, B.A., Sen, S. Nat. Genet. (2004) [Pubmed]
  8. Polymorphisms of the AURKA (STK15/Aurora Kinase) Gene and Breast Cancer Risk (United States). Cox, D.G., Hankinson, S.E., Hunter, D.J. Cancer Causes Control (2006) [Pubmed]
  9. A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines. Sen, S., Zhou, H., White, R.A. Oncogene (1997) [Pubmed]
  10. Breast cancer risk associated with genotypic polymorphism of the mitosis-regulating gene Aurora-A/STK15/BTAK. Lo, Y.L., Yu, J.C., Chen, S.T., Yang, H.C., Fann, C.S., Mau, Y.C., Shen, C.Y. Int. J. Cancer (2005) [Pubmed]
  11. Endothelial Nitric Oxide Synthase (Glu298Asp) Polymorphism is an Independent Risk Factor for Migraine with Aura. Borroni, B., Rao, R., Liberini, P., Venturelli, E., Cossandi, M., Archetti, S., Caimi, L., Padovani, A. Headache (2006) [Pubmed]
  12. Amplification and overexpression of aurora kinase A (AURKA) in immortalized human ovarian epithelial (HOSE) cells. Chung, C.M., Man, C., Jin, Y., Jin, C., Guan, X.Y., Wang, Q., Wan, T.S., Cheung, A.L., Tsao, S.W. Mol. Carcinog. (2005) [Pubmed]
  13. Novel genes implicated in embryonal, alveolar, and pleomorphic rhabdomyosarcoma: a cytogenetic and molecular analysis of primary tumors. Goldstein, M., Meller, I., Issakov, J., Orr-Urtreger, A. Neoplasia (2006) [Pubmed]
  14. 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]
  15. MBD3 and HDAC1, two components of the NuRD complex, are localized at Aurora-A-positive centrosomes in M phase. Sakai, H., Urano, T., Ookata, K., Kim, M.H., Hirai, Y., Saito, M., Nojima, Y., Ishikawa, F. J. Biol. Chem. (2002) [Pubmed]
  16. AURKA amplification, chromosome instability, and centrosome abnormality in human pancreatic carcinoma cells. Zhu, J., Abbruzzese, J.L., Izzo, J., Hittelman, W.N., Li, D. Cancer Genet. Cytogenet. (2005) [Pubmed]
  17. Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/- cells. Meraldi, P., Honda, R., Nigg, E.A. EMBO J. (2002) [Pubmed]
  18. Aurora-A kinase regulates telomerase activity through c-Myc in human ovarian and breast epithelial cells. Yang, H., Ou, C.C., Feldman, R.I., Nicosia, S.V., Kruk, P.A., Cheng, J.Q. Cancer Res. (2004) [Pubmed]
  19. Physical and functional interactions between mitotic kinases during polyploidization and megakaryocytic differentiation. Huang, X., Ruan, Q., Fang, Y., Traganos, F., Darzynkiewicz, Z., Dai, W. Cell Cycle (2004) [Pubmed]
  20. Aurora kinases. Bolanos-Garcia, V.M. Int. J. Biochem. Cell Biol. (2005) [Pubmed]
  21. Targeting aurora2 kinase in oncogenesis: a structural bioinformatics approach to target validation and rational drug design. Vankayalapati, H., Bearss, D.J., Saldanha, J.W., Muñoz, R.M., Rojanala, S., Von Hoff, D.D., Mahadevan, D. Mol. Cancer Ther. (2003) [Pubmed]
  22. Aurora-A abrogation of p53 DNA binding and transactivation activity by phosphorylation of serine 215. Liu, Q., Kaneko, S., Yang, L., Feldman, R.I., Nicosia, S.V., Chen, J., Cheng, J.Q. J. Biol. Chem. (2004) [Pubmed]
  23. The centrosomal kinase Aurora-A/STK15 interacts with a putative tumor suppressor NM23-H1. Du, J., Hannon, G.J. Nucleic Acids Res. (2002) [Pubmed]
  24. CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function. Kunitoku, N., Sasayama, T., Marumoto, T., Zhang, D., Honda, S., Kobayashi, O., Hatakeyama, K., Ushio, Y., Saya, H., Hirota, T. Dev. Cell (2003) [Pubmed]
  25. Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human. Ewart-Toland, A., Briassouli, P., de Koning, J.P., Mao, J.H., Yuan, J., Chan, F., MacCarthy-Morrogh, L., Ponder, B.A., Nagase, H., Burn, J., Ball, S., Almeida, M., Linardopoulos, S., Balmain, A. Nat. Genet. (2003) [Pubmed]
  26. Human TPX2 is required for targeting Aurora-A kinase to the spindle. Kufer, T.A., Silljé, H.H., Körner, R., Gruss, O.J., Meraldi, P., Nigg, E.A. J. Cell Biol. (2002) [Pubmed]
  27. Structural basis of Aurora-A activation by TPX2 at the mitotic spindle. Bayliss, R., Sardon, T., Vernos, I., Conti, E. Mol. Cell (2003) [Pubmed]
  28. Phosphorylation of CDC25B by Aurora-A at the centrosome contributes to the G2-M transition. Dutertre, S., Cazales, M., Quaranta, M., Froment, C., Trabut, V., Dozier, C., Mirey, G., Bouché, J.P., Theis-Febvre, N., Schmitt, E., Monsarrat, B., Prigent, C., Ducommun, B. J. Cell. Sci. (2004) [Pubmed]
  29. Phosphorylation and stabilization of HURP by Aurora-A: implication of HURP as a transforming target of Aurora-A. Yu, C.T., Hsu, J.M., Lee, Y.C., Tsou, A.P., Chou, C.K., Huang, C.Y. Mol. Cell. Biol. (2005) [Pubmed]
  30. NDEL1 phosphorylation by Aurora-A kinase is essential for centrosomal maturation, separation, and TACC3 recruitment. Mori, D., Yano, Y., Toyo-oka, K., Yoshida, N., Yamada, M., Muramatsu, M., Zhang, D., Saya, H., Toyoshima, Y.Y., Kinoshita, K., Wynshaw-Boris, A., Hirotsune, S. Mol. Cell. Biol. (2007) [Pubmed]
  31. The centrosomal protein Lats2 is a phosphorylation target of Aurora-A kinase. Toji, S., Yabuta, N., Hosomi, T., Nishihara, S., Kobayashi, T., Suzuki, S., Tamai, K., Nojima, H. Genes Cells (2004) [Pubmed]
  32. Aurora-A induces cell survival and chemoresistance by activation of Akt through a p53-dependent manner in ovarian cancer cells. Yang, H., He, L., Kruk, P., Nicosia, S.V., Cheng, J.Q. Int. J. Cancer (2006) [Pubmed]
  33. Overexpression and amplification of Aurora-A in hepatocellular carcinoma. Jeng, Y.M., Peng, S.Y., Lin, C.Y., Hsu, H.C. Clin. Cancer Res. (2004) [Pubmed]
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