Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The cellular geography of Aurora kinases

Nature Reviews Molecular Cell Biology volume 4, pages 842–854 (2003)Cite this article

Key Points

  • The Aurora family of conserved serine/threonine kinases perform essential functions during cell division. The three mammalian paralogues are very similar in sequence, but differ significantly in their localization, function, substrates and regulatory partners.

  • Aurora A is mainly associated with the spindle poles during mitosis, where it is required for centrosome separation and maturation. Spindle assembly requires that targeting protein for XKLP 2 (TPX2) targets Aurora A to spindle pole microtubules through a mechanism that requires Ran–GTP. Aurora A also functions in meiosis, promoting oocyte maturation, polar-body extrusion, spindle positioning and exit from metaphase I.

  • Regulation of Aurora A occurs through phosphorylation/dephosphorylation and degradation. Protein phosphatase 1 negatively regulates Aurora and this interaction is modulated by TPX2. The Cdh1/Fizzy-related form of anaphase-promoting complex/cyclosome (APC/C) targets Aurora for degradation in late mitosis.

  • Aurora B is a chromosomal-passenger protein with multiple functions in mitosis. Inner centromere protein (INCENP) and survivin, two other components of the passenger complex, function as targeting and regulatory factors for the kinase. Aurora B is required for phosphorylation of histone 3, targeting of condensin and normal chromosome compaction. It has also been recently shown to be essential for chromosome biorentation, kinetochore–microtubule interactions and the spindle-assembly checkpoint.

  • Aurora B is essential for completion of cytokinesis. Myosin II regulatory chain, vimentin, desmin and glial fibrillary acidic protein are among its cleavage furrow substrates. Aurora B phosphorylates MgcRacGAP transforming it into an activator of RhoA in the contractile ring.

  • Much less is known about Aurora-C kinases, other than that they seem to be preferentially expressed in meiotic cells — they are not discussed here in detail.

  • Misexpression of Aurora kinases is linked to cancer, but their possible role in carcinogenesis is yet to be elucidated.

  • During the cell cycle, Aurora kinases travel to their subcellular targets aided by their binding partner-substrates, INCENP, survivin and TPX2. This provides an additional level of regulation that might be essential for the choreography of mitotic events.

Abstract

Aurora is the name given to a family of highly conserved protein kinases with essential roles in many aspects of cell division. Yeasts have a single Aurora kinase, whereas mammals have three: Aurora A, B and C. During mitosis, Aurora kinases regulate the structure and function of the cytoskeleton and chromosomes and the interactions between these two at the kinetochore. They also regulate signalling by the spindle-assembly checkpoint pathway and cytokinesis. Perturbation of Aurora kinase expression or function might lead to cancer.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The relationships between the kinase domains of the Aurora kinases.
Figure 2: Structure of the Aurora kinases.
Figure 3: Localization of Aurora kinases.
Figure 4: Regulation of Aurora-A activity by Ran–GTP and TPX2.
Figure 5: Role of Aurora B in promoting chromosome bi-orientation on the mitotic spindle.
Figure 6: Some of the known Aurora-B substrates in mitotic cells.
Figure 7: Aurora A and cancer.

Similar content being viewed by others

References

  1. Glover, D. M., Leibowitz, M. H., McLean, D. A. & Parry, H. Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles. Cell 81, 95–105 (1995).

    CAS  PubMed  Google Scholar 

  2. Sunkel, C. E. & Glover, D. M. Polo, a mitotic mutant of Drosophila displaying abnormal spindle poles. J. Cell Sci. 89, 25–38 (1988).

    PubMed  Google Scholar 

  3. Chan, C. S. & Botstein, D. Isolation and characterization of chromosome-gain and increase-in-ploidy mutants in yeast. Genetics 135, 677–691 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Petersen, J., Paris, J., Willer, M., Philippe, M. & Hagan, I. M. The S. pombe aurora-related kinase Ark1 associates with mitotic structures in a stage dependent manner and is required for chromosome segregation. J. Cell Sci. 114, 4371–4384 (2001).

    CAS  PubMed  Google Scholar 

  5. Leverson, J. D., Huang, H. K., Forsburg, S. L. & Hunter, T. The Schizosaccharomyces pombe Aurora-related kinase Ark1 interacts with the inner centromere protein Pic1 and mediates chromosome segregation and cytokinesis. Mol. Biol. Cell 13, 1132–1143 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Adams, R. R., Carmena, M. & Earnshaw, W. C. Chromosomal passengers and the (Aurora) ABCs of mitosis. Trends Cell Biol. 11, 49–54 (2001).

    CAS  PubMed  Google Scholar 

  7. Nigg, E. A. Mitotic kinases as regulators of cell division and its checkpoints. Nature Rev. Mol. Cell. Biol. 2, 21–32 (2001).

    CAS  Google Scholar 

  8. Bischoff, J. R. et al. A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J. 17, 3052–3065 (1998). Provides one of the first insights into the link between Aurora kinases and carcinogenesis.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Giet, R. & Prigent, C. Aurora/Ipl1p-related kinases, a new oncogenic family of mitotic serine-threonine kinases. J. Cell Sci. 112, 3591–3601 (1999).

    CAS  PubMed  Google Scholar 

  10. Cheetham, G. M. et al. Crystal structure of aurora-2, an oncogenic serine/threonine kinase. J. Biol. Chem. 277, 42419–42422 (2002).

    CAS  PubMed  Google Scholar 

  11. Nowakowski, J. et al. Structures of the cancer-related Aurora-A, FAK, and EphA2 protein kinases from nanovolume crystallography. Structure 10, 1659–1667 (2002).

    CAS  PubMed  Google Scholar 

  12. Earnshaw, W. C. & Bernat, R. L. Chromosomal passengers: towards an integrated view of mitosis. Chromosoma 100, 139–146 (1990).

    Google Scholar 

  13. Bernard, M., Sanseau, P., Henry, C., Couturier, A. & Prigent, C. Cloning of STK13, a third human protein kinase related to Drosophila aurora and budding yeast Ipl1 that maps on chromosome 19q13.3-ter. Genomics 53, 406–409 (1998).

    CAS  PubMed  Google Scholar 

  14. Tseng, T. C., Chen, S. H., Hsu, Y. P. & Tang, T. K. 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. DNA Cell Biol. 17, 823–833 (1998).

    CAS  PubMed  Google Scholar 

  15. Kimura, M., Matsuda, Y., Yoshioka, T. & Okano, Y. Cell cycle-dependent expression and centrosome localization of a third human aurora/Ipl1-related protein kinase, AIK3. J. Biol. Chem. 274, 7334–7340 (1999).

    CAS  PubMed  Google Scholar 

  16. Hu, H. M., Chuang, C. K., Lee, M. J., Tseng, T. C. & Tang, T. K. Genomic organization, expression, and chromosome localization of a third aurora-related kinase gene, Aie1. DNA Cell Biol. 19, 679–688 (2000).

    CAS  PubMed  Google Scholar 

  17. Schumacher, J. M., Ashcroft, N., Donovan, P. J. & Golden, A. A highly conserved centrosomal kinase, AIR-1, is required for accurate cell cycle progression and segregation of developmental factors in Caenorhabditis elegans embryos. Development 125, 4391–4402 (1998).

    CAS  PubMed  Google Scholar 

  18. Roghi, C. et al. The Xenopus protein kinase pEg2 associates with the centrosome in a cell cycle-dependent manner, binds to the spindle microtubules and is involved in bipolar mitotic spindle assembly. J. Cell Sci. 111, 557–572 (1998).

    CAS  PubMed  Google Scholar 

  19. Sugimoto, K. et al. Molecular dynamics of aurora-A kinase in living mitotic cells simultaneously visualized with histone H3 and nuclear membrane protein importinα. Cell Struct. Funct. 27, 457–467 (2002).

    CAS  PubMed  Google Scholar 

  20. Berdnik, D. & Knoblich, J. A. Drosophila Aurora-A is required for centrosome maturation and actin-dependent asymmetric protein localization during mitosis. Curr. Biol. 12, 640–647 (2002). This describes a role for Aurora A in asymmetric cell division and examines the dynamics of Aurora-A association with centrosomes.

    CAS  PubMed  Google Scholar 

  21. Wittmann, T., Wilm, M., Karsenti, E. & Vernos, I. TPX2, a novel Xenopus MAP involved in spindle pole organization. J. Cell Biol. 149, 1405–1418 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Gruss, O. J. et al. Chromosome-induced microtubule assembly mediated by TPX2 is required for spindle formation in HeLa cells. Nature Cell Biol. 4, 871–879 (2002).

    CAS  PubMed  Google Scholar 

  23. Giet, R. & Prigent, C. The non-catalytic domain of the Xenopus laevis aurora A kinase localises the protein to the centrosome. J. Cell Sci. 114, 2095–2104 (2001).

    CAS  PubMed  Google Scholar 

  24. Giet, R. et al. Drosophila Aurora A kinase is required to localize D-TACC to centrosomes and to regulate astral microtubules. J. Cell Biol. 156, 437–451 (2002). RNAi analysis confirms a role for Aurora A in centrosome maturation and separation.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Kufer, T. A. et al. Human TPX2 is required for targeting Aurora-A kinase to the spindle. J. Cell Biol. 158, 617–623 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Hannak, E., Kirkham, M., Hyman, A. A. & Oegema, K. Aurora-A kinase is required for centrosome maturation in Caenorhabditis elegans. J. Cell Biol. 155, 1109–1116 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Giet, R., Uzbekov, R., Cubizolles, F., Le Guellec, K. & Prigent, C. The Xenopus laevis aurora-related protein kinase pEg2 associates with and phosphorylates the kinesin-related protein XlEg5. J. Biol. Chem. 274, 15005–15013 (1999).

    CAS  PubMed  Google Scholar 

  28. Tsai, M. Y. et al. A Ran signalling pathway mediated by the mitotic kinase Aurora A in spindle assembly. Nature Cell Biol. 5, 242–248 (2003). This study shows that TPX2 activates Aurora-A kinase, and proposes that Aurora A might be an important downstream target of Ran–GTP in promoting mitotic spindle assembly.

    CAS  PubMed  Google Scholar 

  29. Wilde, A. & Zheng, Y. Stimulation of microtubule aster formation and spindle assembly by the small GTPase Ran. Science 284, 1359–1362 (1999).

    CAS  PubMed  Google Scholar 

  30. Kalab, P., Pu, R. T. & Dasso, M. The ran GTPase regulates mitotic spindle assembly. Curr. Biol. 9, 481–484 (1999).

    CAS  PubMed  Google Scholar 

  31. Carazo-Salas, R. E. et al. Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation. Nature 400, 178–181 (1999).

    CAS  PubMed  Google Scholar 

  32. Eyers, P. A., Erikson, E., Chen, L. G. & Maller, J. L. A novel mechanism for activation of the protein kinase aurora a. Curr. Biol. 13, 691–697 (2003). This study shows that TPX2 activates Aurora-A kinase in part by blocking the inactivation of the kinase by protein phosphatase 1.

    CAS  PubMed  Google Scholar 

  33. Andresson, T. & Ruderman, J. V. The kinase Eg2 is a component of the Xenopus oocyte progesterone-activated signaling pathway. EMBO J. 17, 5627–5637 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Mendez, R. et al. Phosphorylation of CPE binding factor by Eg2 regulates translation of c-mos mRNA. Nature 404, 302–307 (2000). This describes the involvement of Aurora A in cell-cycle regulation by regulating poly(A)-dependent translation.

    CAS  PubMed  Google Scholar 

  35. Frank-Vaillant, M. et al. Progesterone regulates the accumulation and the activation of Eg2 kinase in Xenopus oocytes. J. Cell Sci. 113, 1127–1138 (2000).

    CAS  PubMed  Google Scholar 

  36. Maton, G. et al. Cdc2–Cyclin B triggers H3 kinase activation of Aurora-A in Xenopus oocytes. J. Biol. Chem. 278, 21439–21449 (2003).

    CAS  PubMed  Google Scholar 

  37. Schumacher, J. M., Golden, A. & Donovan, P. J. AIR-2: An Aurora/Ipl1-related protein kinase associated with chromosomes and midbody microtubules is required for polar body extrusion and cytokinesis in Caenorhabditis elegans embryos. J. Cell Biol. 143, 1635–1646 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Castro, A., Mandart, E., Lorca, T. & Galas, S. Involvement of Aurora A kinase during meiosis I–II transition in Xenopus oocytes. J. Biol. Chem. 278, 2236–2241 (2003).

    CAS  PubMed  Google Scholar 

  39. Littlepage, L. E. et al. Identification of phosphorylated residues that affect the activity of the mitotic kinase Aurora-A. Proc. Natl Acad. Sci. USA 99, 15440–15445 (2002). Systematic analysis of the residues that are relevant for regulation of Aurora-A kinase.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Walter, A. O., Seghezzi, W., Korver, W., Sheung, J. & Lees, E. The mitotic serine/threonine kinase Aurora2/AIK is regulated by phosphorylation and degradation. Oncogene 19, 4906–4916 (2000).

    CAS  PubMed  Google Scholar 

  41. Cheeseman, I. M. et al. Phospho-regulation of kinetochore-microtubule attachments by the Aurora kinase Ipl1p. Cell 111, 163–172 (2002). This is the most thorough study yet of the protein targets of the Aurora kinase Ipl1.

    CAS  PubMed  Google Scholar 

  42. Francisco, L., Wang, W. & Chan, C. S. Type 1 protein phosphatase acts in opposition to IpL1 protein kinase in regulating yeast chromosome segregation. Mol. Cell. Biol. 14, 4731–4740 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Katayama, H., Zhou, H., Li, Q., Tatsuka, M. & Sen, S. Interaction and feedback regulation between STK15/BTAK/Aurora-A kinase and protein phosphatase 1 through mitotic cell division cycle. J. Biol. Chem. 276, 46219–46224 (2001).

    CAS  PubMed  Google Scholar 

  44. Murnion, M. E. et al. Chromatin-associated protein phosphatase 1 regulates Aurora-B and histone H3 phosphorylation. J. Biol. Chem. 276, 26656–26665 (2001).

    CAS  PubMed  Google Scholar 

  45. Honda, K. et al. Degradation of human Aurora2 protein kinase by the anaphase-promoting complex-ubiquitin-proteasome pathway. Oncogene 19, 2812–2819 (2000).

    CAS  PubMed  Google Scholar 

  46. Castro, A. et al. APC/Fizzy-Related targets Aurora-A kinase for proteolysis. EMBO Rep. 3, 457–462 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Castro, A. et al. The D-Box-activating domain (DAD) is a new proteolysis signal that stimulates the silent D-Box sequence of Aurora-A. EMBO Rep. 3, 1209–1214 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Littlepage, L. E. & Ruderman, J. V. 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. Genes Dev. 16, 2274–2285 (2002). References 46 and 48 do a good job of dissecting the complexities of Aurora-A regulation by the APC/C.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Kiat, L. S., Hui, K. M. & Gopalan, G. Aurora-A kinase interacting protein (AIP), a novel negative regulator of human Aurora-A kinase. J. Biol. Chem. 277, 45558–45565 (2002).

    CAS  PubMed  Google Scholar 

  50. Terada, Y. et al. AIM-1: a mammalian midbody-associated protein required for cytokinesis. EMBO J. 17, 667–676 (1998). One of the first reports showing the requirement of Aurora B for cytokinesis.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Adams, R. R., Maiato, H., Earnshaw, W. C. & Carmena, M. Essential roles of Drosophila inner centromere protein (INCENP) and Aurora-B in histone H3 phosphorylation, metaphase chromosome alignment, kinetochore disjunction, and chromosome segregation. J. Cell Biol. 153, 865–880 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Murata-Hori, M., Tatsuka, M. & Wang, Y. L. Probing the dynamics and functions of Aurora B kinase in living cells during mitosis and cytokinesis. Mol. Biol. Cell 13, 1099–1108 (2002). Examines the dynamic behaviour of Aurora-B kinase in vivo using green-fluorescent-protein-labelled protein.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Nicklas, R. B. & Staehly, C. A. Chromosome micromanipulation. I. The mechanics of chromosome attachment to the spindle. Chromosoma 21, 1–16 (1967).

    CAS  PubMed  Google Scholar 

  54. Nicklas, R. B., Wards, S. C. & Gorbsky, G. J. Kinetochore chemistry is sensitive to tension and may link mitotic forces for a cell cycle checkpoint. J. Cell Biol. 130, 929–939 (1995).

    CAS  PubMed  Google Scholar 

  55. Tanaka, T. U. et al. Evidence that the Ipl1–Sli15 (Aurora kinase–INCENP) complex promotes chromosome bi-orientation by altering kinetochore-spindle pole connections. Cell 108, 317–329 (2002). This paper was the first to propose that Ipl1 might be involved in the resolution of syntelic chromsome attachments.

    CAS  PubMed  Google Scholar 

  56. Kallio, M. J., McCleland, M. L., Stukenberg, P. T. & Gorbsky, G. J. Inhibition of aurora B kinase blocks chromosome segregation, overrides the spindle checkpoint, and perturbs microtubule dynamics in mitosis. Curr. Biol. 12, 900–905 (2002). Antibody injection is used to identify some of the many functions of Aurora B in mammalian cells.

    CAS  PubMed  Google Scholar 

  57. Ditchfield, C. et al. Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2 and Cenp-E to kinetochores. J. Cell Biol. 161, 267–280 (2003). This description of a small-molecule inhibitor of Aurora B identifies a role for the kinase in the spindle-assembly checkpoint when the checkpoint is activated in the presence of microtubules by altering tension within the spindle.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Hauf, S. et al. The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint. J. Cell Biol. 161, 281–294 (2003). This description of a second small-molecule inhibitor of Aurora B provides the best evidence to date that the kinase is involved in the resolution of syntelic chromosomal attachments during prometaphase.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Murata-Hori, M. & Wang, Y. The kinase activity of Aurora B is required for kinetochore–microtubule interactions during mitosis. Curr. Biol. 12, 894–899 (2002).

    CAS  PubMed  Google Scholar 

  60. Biggins, S. et al. The conserved protein kinase Ipl1 regulates microtubule binding to kinetochores in budding yeast. Genes Dev. 13, 532–544 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Kang, J. et al. Functional cooperation of Dam1, Ipl1, and the inner centromere protein (INCENP)-related protein Sli15 during chromosome segregation. J. Cell Biol. 155, 763–774 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Buvelot, S., Tatsutani, S. Y., Vermaak, D. & Biggins, S. The budding yeast Ipl1/Aurora protein kinase regulates mitotic spindle disassembly. J. Cell Biol. 160, 329–339 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Shang, C. et al. Kinetochore protein interactions and their regulation by the Aurora kinase Ipl1p. Mol. Biol. Cell 14, 3342–3355 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Honda, R., Korner, R. & Nigg, E. A. Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis. Mol. Biol. Cell 14, 3325–3341 (2003). A thorough study of the regulation of Aurora-B kinase activity by INCENP and survivin.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Zeitlin, S. G., Shelby, R. D. & Sullivan, K. F. CENP-A is phosphorylated by Aurora B kinase and plays an unexpected role in completion of cytokinesis. J. Cell. Biol. 155, 1147–1157 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Gurley, L. R., D'Anna, J. A., Barham, S. S., Deaven, L. L. & Tobey, R. A. Histone phosphorylation and chromatin structure during mitosis in Chinese hamster cells. Eur. J. Biochem. 84, 1–15 (1978).

    CAS  PubMed  Google Scholar 

  67. Hsu, J. Y. et al. Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes. Cell 102, 279–291 (2000).

    CAS  PubMed  Google Scholar 

  68. Speliotes, E. K., Uren, A., Vaux, D. & Horvitz, H. R. The survivin-like C. elegans BIR-1 protein acts with the Aurora-like kinase AIR-2 to affect chromosomes and the spindle midzone. Mol. Cell 6, 211–223 (2000).

    CAS  PubMed  Google Scholar 

  69. Giet, R. & Glover, D. M. 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, 669–681 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Crosio, C. et al. Mitotic phosphorylation of histone H3: spatio-temporal regulation by mammalian Aurora kinases. Mol. Cell. Biol. 22, 874–885 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. MacCallum, D. E., Losada, A., Kobayashi, R. & Hirano, T. ISWI remodeling complexes in Xenopus egg extracts: identification as major chromosomal components that are regulated by INCENP-aurora B. Mol. Biol. Cell 13, 25–39 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Goto, H. et al. Identification of a novel phosphorylation site on histone H3 coupled with mitotic chromosome condensation. J. Biol. Chem. 274, 25543–25549 (1999).

    CAS  PubMed  Google Scholar 

  73. Goto, H., Yasui, Y., Nigg, E. A. & Inagaki, M. Aurora-B phosphorylates Histone H3 at serine28 with regard to the mitotic chromosome condensation. Genes Cells 7, 11–17 (2002).

    CAS  PubMed  Google Scholar 

  74. Giet, R. & Prigent, C. The Xenopus laevis aurora/Ip11p-related kinase pEg2 participates in the stability of the bipolar mitotic spindle. Exp. Cell Res. 258, 145–151 (2000).

    CAS  PubMed  Google Scholar 

  75. Hirano, T. The ABCs of SMC proteins: two-armed ATPases for chromosome condensation, cohesion, and repair. Genes Dev. 16, 399–414 (2002).

    CAS  PubMed  Google Scholar 

  76. Petersen, J. & Hagan, I. M. S. pombe Aurora kinase/survivin is required for chromosome condensation and the spindle checkpoint attachment response. Curr. Biol. 13, 590–597 (2003). This study uses yeast genetics to show a role for Aurora B and its associated protein survivin in the spindle-assembly checkpoint.

    CAS  PubMed  Google Scholar 

  77. Kaitna, S., Pasierbek, P., Jantsch, M., Loidl, J. & Glotzer, M. The Aurora B kinase AIR-2 regulates kinetochores during mitosis and is required for separation of homologous chromosomes during meiosis. Curr. Biol. 12, 798–812 (2002).

    CAS  PubMed  Google Scholar 

  78. Hagstrom, K. A., Holmes, V. F., Cozzarelli, N. R. & Meyer, B. J. C. elegans condensin promotes mitotic chromosome architecture, centromere organization, and sister chromatid segregation during mitosis and meiosis. Genes Dev. 16, 729–742 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Rogers, E., Bishop, J. D., Waddle, J. A., Schumacher, J. M. & Lin, R. The aurora kinase AIR-2 functions in the release of chromosome cohesion in Caenorhabditis elegans meiosis. J. Cell Biol. 157, 219–229 (2002). This provides important insights into the role of Aurora B in chromosome segregation in meiosis.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Sonoda, E. et al. Scc1/Rad21/Mcd1 is required for sister chromatid cohesion and kinetochore function in vertebrate cells. Dev. Cell 1, 759–770 (2001).

    CAS  PubMed  Google Scholar 

  81. Mackay, A. M., Ainsztein, A., Eckley, D. M. & Earnshaw, W. C. A dominant mutant of inner centromere protein (INCENP), a chromosomal protein, disrupts prometaphase congression and cytokinesis. J. Cell Biol. 140, 991–1002 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Adams, R. R. et al. INCENP binds the aurora-related kinase AIRK2 and is required to target it to chromosomes, the central spindle and cleavage furrow. Curr. Biol 10, 1075–1078 (2000).

    CAS  PubMed  Google Scholar 

  83. Kaitna, S., Mendoza, M., Jantsch-Plunger, V. & Glotzer, M. Incenp and an Aurora-like kinase form a complex essential for chromosome segregation and efficient completion of cytokinesis. Curr. Biol. 10, 1172–1181 (2000).

    CAS  PubMed  Google Scholar 

  84. Severson, A. F., Hamill, D. R., Carter, J. C., Schumacher, J. & Bowerman, B. The aurora-related kinase AIR-2 recruits ZEN-4/CeMKLP1 to the mitotic spindle at metaphase and is required for cytokinesis. Curr. Biol. 10, 1162–1171 (2000).

    CAS  PubMed  Google Scholar 

  85. Murata-Hori, M. et al. Myosin II regulatory light chain as a novel substrate for AIM-1, an aurora/Ipl1p-related kinase from rat. J. Biochem. (Tokyo) 128, 903–907 (2000).

    CAS  Google Scholar 

  86. Goto, H. et al. Aurora-B regulates the cleavage furrow-specific vimentin phosphorylation in the cytokinetic process. J. Biol. Chem. 278, 8526–8530 (2003).

    CAS  PubMed  Google Scholar 

  87. Kawajiri, A. et al. Functional significance of the specific sites phosphorylated in desmin at cleavage furrow: Aurora-B may phosphorylate and regulate Type III intermediate filaments during cytokinesis coordinatedly with Rho-kinase. Mol. Biol. Cell 14, 1489–1500 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Jantsch-Plunger, V. et al. CYK-4: A Rho family GTPase activating protein (GAP) required for central spindle formation and cytokinesis. J. Cell Biol. 149, 1391–1404 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Minoshima, Y., et al. Phosphorylation by Aurora B converts MgcRacGAP to a RhoGAP during cytokinesis. Dev. Cell 4, 549–560 (2003). An elegant study that identifies a new substrate for Aurora B and shows how the kinase might participate in the regulation of cytokinesis.

    CAS  PubMed  Google Scholar 

  90. Kishi, K., Sasaki, T., Kuroda, S., Itoh, T. & Takai, Y. Regulation of cytoplasmic division of Xenopus embryo by rho p21 and its inhibitory GDP/GTP exchange protein (rho GDI). J. Cell Biol. 120, 1187–1195 (1993).

    CAS  PubMed  Google Scholar 

  91. Mabuchi, I. et al. A rho-like protein is involved in the organisation of the contractile ring in dividing sand dollar eggs. Zygote 1, 325–331 (1993).

    CAS  PubMed  Google Scholar 

  92. Biggins, S. & Murray, A. W. The budding yeast protein kinase Ipl1/Aurora allows the absence of tension to activate the spindle checkpoint. Genes Dev. 15, 3118–3129 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Carvalho, A., Carmena, M., Sambade, C., Earnshaw, W. C. & Wheatley, S. P. Survivin is required for stable checkpoint activation in taxol-treated HeLa cells. J. Cell Sci. 116, 2987–2998 (2003).

    CAS  PubMed  Google Scholar 

  94. Lens, S. M. A. et al. Survivin is required for a sustained spindle checkpoint arrest in response to lack of tension. EMBO J. 22, 2934–2947 (2003). References 93 and 94 use RNAi technology to show that survivin is required for the spindle-assembly checkpoint in the presence of microtubules, and for BubR1 targeting to the kinetochore.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Sugiyama, K. et al. Aurora-B associated protein phosphatases as negative regulators of kinase activation. Oncogene 21, 3103–3111 (2002).

    CAS  PubMed  Google Scholar 

  96. Wheatley, S. P., Carvalho, A., Vagnarelli, P. & Earnshaw, W. C. INCENP is required for proper targeting of survivin to the centromeres and the anaphase spindle during mitosis. Curr. Biol. 11, 886–890 (2001).

    CAS  PubMed  Google Scholar 

  97. Bolton, M. A. et al. Aurora B kinase exists in a complex with survivin and INCENP and its kinase activity is stimulated by survivin binding and phosphorylation. Mol. Biol. Cell 13, 3064–3077 (2002). A thorough study of the regulation of Aurora-B kinase activity by INCENP and survivin.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Wheatley, S. P., Kandels-Lewis, S. E., Adams, R. R., Ainsztein, A. M. & Earnshaw, W. C. INCENP binds directly to tubulin and requires dynamic microtubules to target to the cleavage furrow. Exp. Cell. Res. 262, 122–127 (2001).

    CAS  PubMed  Google Scholar 

  99. Ainsztein, A. M., Kandels-Lewis, S. E., Mackay, A. M. & Earnshaw, W. C. INCENP centromere and spindle targeting: identification of essential conserved motifs and involvement of heterochromatin protein HP1. J. Cell Biol. 143, 1763–1774 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Terada, Y., Katayama, H., Tatsuka, M. & Kuriyama, R. AIM-1 regulates onset of cytokinesis by targeting INCENP to midzone and midbody. Mol. Biol. Cell 11S, 343a (2000).

    Google Scholar 

  101. Bishop, J. D. & Schumacher, J. M. Phosphorylation of the carboxyl terminus of inner centromere protein (INCENP) by the Aurora B kinase stimulates Aurora B kinase activity. J. Biol. Chem. 277, 27577–27580 (2002). Provided a clear demonstration that INCENP phosphorylation by Aurora B is part of a feedback loop that stimulates kinase activity.

    CAS  PubMed  Google Scholar 

  102. Deveraux, Q. L. & Reed, J. C. IAP family proteins — suppressors of apoptosis. Genes Dev. 13, 239–252 (1999).

    CAS  PubMed  Google Scholar 

  103. Uren, A. G. et al. Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype. Curr. Biol. 10, 1319–1328 (2000).

    CAS  PubMed  Google Scholar 

  104. Chen, J. et al. Survivin enhances Aurora-B kinase activity and localizes Aurora-B in human cells. J. Biol. Chem. 278, 486–490 (2003).

    CAS  PubMed  Google Scholar 

  105. Morishita, J. et al. Bir1/Cut17 moving from chromosome to spindle upon the loss of cohesion is required for condensation, spindle elongation and repair. Genes Cells 6, 743–763 (2001).

    CAS  PubMed  Google Scholar 

  106. Martineau-Thuillier, S., Andreassen, P. R. & Margolis, R. L. Colocalization of TD-60 and INCENP throughout G2 and mitosis: evidence for their possible interaction in signalling cytokinesis. Chromosoma (Berl.) 107, 461–470 (1998).

    CAS  Google Scholar 

  107. Mollinari, C. et al. The mammalian passenger protein TD-60 is an RCC1 family member with an essential role in prometaphase to metaphase progression. Dev. Cell 5, 295–307 (2003).

    CAS  PubMed  Google Scholar 

  108. Ohi, R., Coughlin, M. L., Lane, W. S. & Mitchison, T. J. An inner centromere protein that stimulates the microtubule depolymerizing activity of a KinI kinesin. Dev. Cell 5, 309–321 (2003).

    CAS  PubMed  Google Scholar 

  109. Romano, A. et al. CSC-1: a subunit of the Aurora B kinase complex that binds to the survivin-like protein BIR-1 and the incenp-like protein ICP-1. J. Cell Biol. 161, 229–236 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Tatsuka, M. et al. Multinuclearity and increased ploidy caused by overexpression of the aurora- and Ipl1-like midbody-associated protein mitotic kinase in human cancer cells. Cancer Res. 58, 4811–4816 (1998).

    CAS  PubMed  Google Scholar 

  111. Takahashi, T. et al. Centrosomal kinases, HsAIRK1 and HsAIRK3, are overexpressed in primary colorectal cancers. Jpn. J. Cancer Res. 91, 1007–1014 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Zhou, H. et al. Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nature Genet. 20, 189–193 (1998).

    CAS  PubMed  Google Scholar 

  113. Tanner, M. M. et al. Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer. Clin. Cancer Res. 6, 1833–1839 (2000).

    CAS  PubMed  Google Scholar 

  114. Boveri, T. Zur Frage der Entstehung maligner Tumoren (Fischer Verlag, Jena, 1914).

    Google Scholar 

  115. Doxsey, S. Duplicating dangerously: linking centrosome duplication and aneuploidy. Mol. Cell 10, 439–440 (2002).

    CAS  PubMed  Google Scholar 

  116. Meraldi, P., Honda, R. & Nigg, E. A. Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53−/− cells. EMBO J. 21, 483–492 (2002). Presents data indicating that centrosome amplification in response to Aurora kinase overexpression arises as a result of failures in cytokinesis.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Anand, S., Penrhyn-Lowe, S. & Venkitaraman, A. R. AURORA-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol. Cancer Cell 3, 51–62 (2003).

    CAS  PubMed  Google Scholar 

  118. Chen, S. S., Chang, P. C., Cheng, Y. W., Tang, F. M. & Lin, Y. S. Suppression of the STK15 oncogenic activity requires a transactivation-independent p53 function. EMBO J. 21, 4491–4499 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Minn, A. J., Boise, L. H. & Thompson, C. B. Expression of Bcl-xL and loss of p53 can cooperate to overcome a cell cycle checkpoint induced by mitotic spindle damage. Genes Dev. 10, 2621–2631 (1996).

    CAS  PubMed  Google Scholar 

  120. Lanni, J. S. & Jacks, T. Characterization of the p53-dependent postmitotic checkpoint following spindle disruption. Mol. Cell. Biol. 18, 1055–1064 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Khan, S. H. & Wahl, G. M. p53 and pRb prevent rereplication in response to microtubule inhibitors by mediating a reversible G1 arrest. Cancer Res. 58, 396–401 (1998).

    CAS  PubMed  Google Scholar 

  122. Casenghi, M. et al. p53-independent apoptosis and p53-dependent block of DNA rereplication following mitotic spindle inhibition in human cells. Exp. Cell Res. 250, 339–350 (1999).

    CAS  PubMed  Google Scholar 

  123. Andreassen, P. R., Lohez, O. D., Lacroix, F. B. & Margolis, R. L. Tetraploid state induces p53-dependent arrest of nontransformed mammalian cells in G1. Mol. Biol. Cell 12, 1315–1328 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Gigoux, V., L'Hoste, S., Raynaud, F., Camonis, J. & Garbay, C. Identification of Aurora kinases as RasGAP Src homology 3 domain-binding proteins. J. Biol. Chem. 277, 23742–23746 (2002).

    CAS  PubMed  Google Scholar 

  125. Ota, T. et al. Increased mitotic phosphorylation of histone H3 attributable to AIM-1/Aurora-B overexpression contributes to chromosome number instability. Cancer Res. 62, 5168–5177 (2002).

    CAS  PubMed  Google Scholar 

  126. Gautier, J., Norbury, C., Lohka, M., Nurse, P. & Maller, J. Purified maturation-promoting factor contains the product of a Xenopus homolog of the fission yeast cell cycle control gene cdc2+. Cell 54, 433–439 (1988).

    CAS  PubMed  Google Scholar 

  127. Lohka, M., Hayes, M. K. & Maller, J. L. Purification of maturation-promoting factor, an intracellular regulator of early mitotic events. Proc. Natl Acad. Sci. USA 85, 3009–3013 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Pavletich, N. P. Mechanisms of cyclin-dependent kinase regulation: structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors. J. Mol. Biol. 287, 821–828 (1999).

    CAS  PubMed  Google Scholar 

  129. Kufer, T. A. et al. Human TPX2 is required for targeting Aurora-A kinase to the spindle. J. Cell Biol. 158, 617–623 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors want to thank M. O. Lombardia, University of York, for his generous help and advice on the analysis and modelling of the structural similarities of the kinase domains and for his contribution to figures 1 and 2. Work in the W.C.E. laboratory is supported by The Wellcome Trust, of which W.C.E. is a Principal Research Fellow.

Author information

Authors and Affiliations

  1. Wellcome Trust Centre for Cell Biology, Institute for Cell and Molecular Biology, Kings Buildings, University of Edinburgh, Mayfield Road, Edinburgh, EH9 3JR, Scotland, UK

    Mar Carmena & William C. Earnshaw

Authors
  1. Mar Carmena
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William C. Earnshaw
    View author publications

    You can also search for this author in PubMed Google Scholar

Related links

Related links

DATABASES

FlyBase

aurora

D-TACC

LocusLink

Aurora A

Aurora B

Aurora C

<i>Saccharomyces</i> Genome Database

Bir1

Cse4

Dam1

Ipl1

Ndc10

Sli15

The Sanger Institute, <i>S. pombe</i>

Ark1

Cut17

Rec8

SwissProt

CENP-A

Eg5

MgcRacGAP

Mos

p53

Plk1

survivin

TD-60

TPX2

Glossary

CENTROSOME

The main microtubule-organizing centre of cells.

CHROMOSOME CONDENSATION

On entry into mitosis, chromosomes become compacted or 'condensed'. This is especially apparent in higher eukaryotes.

KINETOCHORE

A proteinaceous structure that connects each chromatid to the spindle microtubules.

MICROTUBULE

A hollow tube, 25 nm in diameter, that is formed by the lateral association of 13 protofilaments, which are themselves polymers of α- and β-tubulin subunits.

PARALOGUES

Genes with related structure and function within the same species.

HETEROCHROMATIN

A condensed form of chromatin containing few expressed genes and often rich in repeated DNA elements. It is commonly, but not exclusively, found around the centromere.

MIDBODY

A dense bundle of microtubules embedded in an electron-dense matrix. This is derived from the central spindle during late telophase and is localized within the intercellular bridge during cytokinesis.

SPINDLE MIDZONE

Organized bundles of antiparallel microtubules that form during anaphase and telophase. Signals from the central spindle are thought to be important for signalling the location of the cleavage furrow.

SPINDLE POLE

The region at the end of the mitotic spindle where minus ends of the microtubules are clustered together as a result of the action of various microtubule motor proteins. In most animal cells, the spindle pole is centered around a centrosome. Plant spindles in somatic cells, however, lack focused centrosomes.

MITOTIC FIGURES

A term used by cytologists to describe mitotic cells visualized under the microscope.

RNA INTERFERENCE

(RNAi). A form of post-transcriptional gene silencing in which expression or transfection of double-stranded RNA induces degradation — by nucleases — of the homologous endogenous transcripts, mimicking the effect of the reduction, or loss, of gene activity.

CENTRIOLE

A cylindrical array of 9 bundles of microtubules (usually triplets in animal cells) with other specialized appendages. Two centrioles, referred to as mother and daughter, are found in the centre of centrosomes in animal cells.

PERICENTRIOLAR MATERIAL

Region of the cytoplasm surrounding the two centrioles in the centrosome. This is the region where microtubule assembly is initiated by γ-tubulin.

γ-TUBULIN

A specialized isoform of tubulin that, together with several associated proteins, forms a ring-like complex that directs the initiation of microtubule assembly.

IMPORTINS

A class of protein discovered because of the ability of the members to act as adaptors and carriers during the import (and export) of proteins across the nuclear envelope. Importins are now known to have a second role in regulating the assembly of the mitotic spindle.

ACTIVATION LOOP

A conserved structural motif in kinase domains, which needs to be phosphorylated for full activation of the kinase.

MPF

(Maturation-promoting factor/M-phase promoting factor). The complex of a B-type cyclin Cks1, and cyclin-dependent kinase 1, which is also referred to as Cdc2 or p34, depending on the species. This is the main enzyme that is responsible for entry into M phase in both meiosis and mitosis.

POLAR BODY

Either of the two small cells, each being formed during the successive divisions of meiosis, that forms as a result of division of a primary oocyte during its development to a mature ovum. The cytoplasm divides unequally during each division — the polar body is much smaller than the developing oocyte. Polar bodies eventually degenerate.

METAPHASE PLATE

The dynamic group of chromosomes positioned roughly midway between spindle poles prior to the onset of anaphase. These chromosomes have formed proper bipolar attachments (that is, their sister chromatids are connected to opposite spindle poles).

PROTEASOME

Protein complex responsible for degrading intracellular proteins that have been tagged for destruction by the addition of ubiquitin.

ASTRAL MICROTUBULES

Microtubules that extend in a radial array outwards from the spindle poles, excluding those microtubules that attach to kinetochores or form part of the organized spindle midzone.

SISTER CHROMATIDS

Chromosomes that have been duplicated during S phase. Sister chromatids are held together by cohesins until metaphase.

CONGRESSION

The movement of correctly attached mitotic chromosomes to the metaphase plate at the midzone of the mitotic spindle.

CONDENSIN

A complex of two SMC (structural maintenance of chromosomes) proteins and three auxiliary subunits that can bind to and supercoil DNA. Condensin directs the binding of other non-histone proteins to mitotic chromosomes, and although not essential for mitotic chromatin condensation, it is essential for the structural integrity of mitotic chromosomes.

CHIASMATA

Connections formed between homologous chromosomes that are thought to be the point of the interchange that is involved in crossing over.

COHESIN

A protein complex that tethers sister chromatids together from the time they are created (during DNA replication) until cohesin cleavage at the onset of anaphase.

CLEAVAGE FURROW

A region of the plasma membrane in higher eukaryotic cells that ingresses to separate the two daughter cells at cytokinesis; contraction in this region is driven by actin and myosin filament interaction.

INTERMEDIATE FILAMENT

A cytoskeletal filament, typically 10 nm in diameter, that occurs in higher eukaryotic cells. The protein composition of intermediate filaments varies between cell types. Examples of intermediate filament proteins are keratins, vimentin and desmin.

ANEUPLOIDY

The ploidy of a cell refers to the number of sets of chromosomes that it contains. Aneuploid karyotypes are those whose chromosome complements are not a simple multiple of the haploid set.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carmena, M., Earnshaw, W. The cellular geography of Aurora kinases. Nat Rev Mol Cell Biol 4, 842–854 (2003). https://doi.org/10.1038/nrm1245

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm1245

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing