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 chromosomal passenger complex (CPC): from easy rider to the godfather of mitosis

Nature Reviews Molecular Cell Biology volume 13, pages 789–803 (2012)Cite this article

Subjects

Key Points

  • The chromosomal passenger complex (CPC) is a 'master controller' of cell division that is formed by a kinase module (Aurora B kinase) and a localization module (the scaffolding protein inner centromere protein (INCENP), survivin and borealin).

  • Multiple post-translational modifications of CPC components contribute to the appropriate localization and regulation of Aurora B activity. Full activation of Aurora B kinase is a complex multistage process that is mediated by the other CPC components and other cell cycle kinases.

  • In early mitosis, CPC recruitment to the inner centromere is mediated by post-translational modifications of two histones: phosphorylation of histone H3 (by haspin kinase) and of histone H2A (by Bub1 kinase). The baculovirus IAP repeat (BIR) domain of survivin recognizes H3 phosphorylated at Thr3. Further enrichment of the CPC at the inner centromere is mediated by Aurora B-dependent regulatory feedback loops.

  • Roles of the CPC in early mitosis include the regulation of chromosome structure, kinetochore–microtubule attachments and the spindle assembly checkpoint.

  • The CPC relocalizes to central spindle microtubules at the onset of anaphase in a highly regulated process that is mediated by a decrease of cyclin-dependent kinase 1 (Cdk1) activity, interaction with the kinesin mitotic kinesin-like protein 2 (Mklp2) and under the control of several phosphatases and Aurora B kinase itself.

  • Functions of the CPC in late mitosis include the formation and stabilization of the spindle midzone in anaphase and the regulation of the contractile ring formation. The CPC has further roles later on in cytokinesis, in which it regulates furrow ingression and the abscission checkpoint.

Abstract

Successful cell division requires the precise and timely coordination of chromosomal, cytoskeletal and membrane trafficking events. These processes are regulated by the competing actions of protein kinases and phosphatases. Aurora B is one of the most intensively studied kinases. In conjunction with inner centromere protein (INCENP), borealin (also known as Dasra) and survivin it forms the chromosomal passenger complex (CPC). This complex targets to different locations at differing times during mitosis, where it regulates key mitotic events: correction of chromosome–microtubule attachment errors; activation of the spindle assembly checkpoint; and construction and regulation of the contractile apparatus that drives cytokinesis. Our growing understanding of the CPC has seen it develop from a mere passenger riding on the chromosomes to one of the main controllers of mitosis.

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: Structure and regulation of the CPC.
Figure 2: Coupling of Aurora B kinase activation to CPC formation and localization.
Figure 3: The CPC produces spatial gradients of Aurora B activity throughout mitosis.
Figure 4: Recruitment of the CPC to centromeres during early mitosis.
Figure 5: CPC relocalization and function in mitotic exit.

Similar content being viewed by others

References

  1. Earnshaw, W. C. & Bernat, R. L. Chromosomal passengers: toward an integrated view of mitosis. Chromosoma 100, 139–146 (1991). The proposal that proteins associated with mitotic chromosomes might integrate both chromosomal and cytoskeletal events in mitosis.

    Article  CAS  PubMed  Google Scholar 

  2. Cooke, C. A., Heck, M. M. & Earnshaw, W. C. The inner centromere protein (INCENP) antigens: movement from inner centromere to midbody during mitosis. J. Cell Biol. 105, 2053–2067 (1987). The original publication describing the identification of INCENP.

    Article  CAS  PubMed  Google Scholar 

  3. 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).

    Article  CAS  PubMed  Google Scholar 

  4. 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). Provides, together with reference 3, the first description of the biochemical complex between Aurora B and INCENP, forming the CPC.

    Article  CAS  PubMed  Google Scholar 

  5. Ruchaud, S., Carmena, M. & Earnshaw, W. C. Chromosomal passengers: conducting cell division. Nature Rev. Mol. Cell. Biol. 8, 798–812 (2007).

    Article  CAS  Google Scholar 

  6. Kelly, A. E. & Funabiki, H. Correcting aberrant kinetochore microtubule attachments: an Aurora B-centric view. Curr. Opin. Cell Biol. 21, 51–58 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. van der Waal, M. S., Hengeveld, R. C., van der Horst, A. & Lens, S. M. Cell division control by the chromosomal passenger complex. 318, 1407–1420 Exp. Cell Res. (2012).

    Article  CAS  PubMed  Google Scholar 

  8. 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). Uses for the first time RNAi to probe the function of the CPC in vivo.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. 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).

    Article  CAS  PubMed  Google Scholar 

  10. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gassmann, R. et al. Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle. J. Cell Biol. 166, 179–191 (2004). First description of borealin and its interaction with survivin.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Vader, G., Kauw, J. J., Medema, R. H. & Lens, S. M. Survivin mediates targeting of the chromosomal passenger complex to the centromere and midbody. EMBO Rep. 7, 85–92 (2006).

    Article  CAS  PubMed  Google Scholar 

  13. 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).

    Article  CAS  PubMed  Google Scholar 

  14. Mackay, A. M. & Earnshaw, W. C. The INCENPs: structural and functional analysis of a family of chromosome passenger proteins. Cold Spring Harb. Symp. Quant. Biol. 58, 697–706 (1993).

    Article  CAS  PubMed  Google Scholar 

  15. Jeyaprakash, A. A., Basquin, C., Jayachandran, U. & Conti, E. Structural basis for the recognition of phosphorylated histone H3 by the survivin subunit of the chromosomal passenger complex. Structure 19, 1625–1634 (2011).

    Article  CAS  PubMed  Google Scholar 

  16. Jeyaprakash, A. A. et al. Structure of a Survivin–Borealin–INCENP core complex reveals how chromosomal passengers travel together. Cell 131, 271–285 (2007). Describes the crystal structure of the three-helix bundle formed by survivin–borealin–INCENP and explores its role in the localization of the CPC.

    Article  CAS  PubMed  Google Scholar 

  17. Song, Z. et al. A single amino acid change (Asp 53 → Ala53) converts survivin from anti-apoptotic to pro-apoptotic. Mol. Biol. Cell 15, 1287–1296 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lens, S. M., Vader, G. & Medema, R. H. The case for Survivin as mitotic regulator. Curr. Opin. Cell Biol. 18, 616–622 (2006).

    Article  CAS  PubMed  Google Scholar 

  19. Yue, Z. et al. Deconstructing Survivin: comprehensive genetic analysis of Survivin function by conditional knockout in a vertebrate cell line. J. Cell Biol. 183, 279–296 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kelly, A. E. et al. Survivin reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B. Science 330, 235–239 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wang, F. et al. Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis. Science 330, 231–235 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Yamagishi, Y., Honda, T., Tanno, Y. & Watanabe, Y. Two histone marks establish the inner centromere and chromosome bi-orientation. Science 330, 239–243 (2010). Describes, together with references 20 and 21, the post-translational modifications of histones that define the inner centromere and that are responsible for the targeting of the CPC to centromeres.

    Article  CAS  PubMed  Google Scholar 

  23. 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). Identifies the original Aurora kinase family member.

    Article  CAS  PubMed  Google Scholar 

  24. Carmena, M., Ruchaud, S. & Earnshaw, W. C. Making the Auroras glow: regulation of Aurora A and B kinase function by interacting proteins. Curr. Opin. Cell Biol. 21, 796–805 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lens, S. M., Voest, E. E. & Medema, R. H. Shared and separate functions of polo-like kinases and aurora kinases in cancer. Nature Rev. Cancer 10, 825–841 (2010).

    Article  CAS  Google Scholar 

  26. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Klein, U. R., Nigg, E. A. & Gruneberg, U. Centromere targeting of the chromosomal passenger complex requires a ternary subcomplex of Borealin, Survivin, and the N-terminal domain of INCENP. Mol. Biol. Cell 17, 2547–2558 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Nozawa, R. S. et al. Human POGZ modulates dissociation of HP1α from mitotic chromosome arms through Aurora B activation. Nature Cell Biol. 12, 719–727 (2010). Shows that the HP1α-binding protein POGZ is required for activation of Aurora B and its dissociation from chromosomes.

    Article  CAS  PubMed  Google Scholar 

  29. Kang, J. et al. Mitotic centromeric targeting of HP1 and its binding to Sgo1 are dispensable for sister-chromatid cohesion in human cells. Mol. Biol. Cell 22, 1181–1190 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Nakajima, Y. et al. Ipl1/Aurora-dependent phosphorylation of Sli15/INCENP regulates CPC–spindle interaction to ensure proper microtubule dynamics. J. Cell Biol. 194, 137–153 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Pereira, G. & Schiebel, E. Separase regulates INCENP–Aurora B anaphase spindle function through Cdc14. Science 302, 2120–2124 (2003).

    Article  CAS  PubMed  Google Scholar 

  32. Mirchenko, L. & Uhlmann, F. Sli15(INCENP) dephosphorylation prevents mitotic checkpoint reengagement due to loss of tension at anaphase onset. Curr. Biol. 20, 1396–1401 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Vazquez-Novelle, M. D. & Petronczki, M. Relocation of the chromosomal passenger complex prevents mitotic checkpoint engagement at anaphase. Curr. Biol. 20, 1402–1407 (2010).

    Article  CAS  PubMed  Google Scholar 

  34. Goto, H. et al. Complex formation of Plk1 and INCENP required for metaphase–anaphase transition. Nature Cell Biol. 8, 180–187 (2006).

    Article  CAS  PubMed  Google Scholar 

  35. Carmena, M. et al. The chromosomal passenger complex activates Polo kinase at centromeres. PLoS Biol. 10, e1001250 (2012). Describes a conserved mechanism of Aurora B activation of Polo kinase at the centromeres mediated by INCENP.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lens, S. M. et al. Uncoupling the central spindle-associated function of the chromosomal passenger complex from its role at centromeres. Mol. Biol. Cell 17, 1897–1909 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Szafer-Glusman, E., Fuller, M. T. & Giansanti, M. G. Role of Survivin in cytokinesis revealed by a separation-of-function allele. Mol. Biol. Cell 22, 3779–3790 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ambrosini, G., Adida, C. & Altieri, D. C. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nature Med. 3, 917–921 (1997).

    Article  CAS  PubMed  Google Scholar 

  39. Uren, A. G. et al. Role for yeast inhibitor of apoptosis (IAP)-like proteins in cell division. Proc. Natl Acad. Sci. USA 96, 10170–10175 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. 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).

    Article  CAS  PubMed  Google Scholar 

  41. Stauber, R. H. et al. Nucleocytoplasmic shuttling and the biological activity of mouse survivin are regulated by an active nuclear export signal. Traffic 7, 1461–1472 (2006).

    Article  CAS  PubMed  Google Scholar 

  42. Connell, C. M., Colnaghi, R. & Wheatley, S. P. Nuclear survivin has reduced stability and is not cytoprotective. J. Biol. Chem. 283, 3289–3296 (2008).

    Article  CAS  PubMed  Google Scholar 

  43. Verdecia, M. A. et al. Structure of the human anti-apoptotic protein survivin reveals a dimeric arrangement. Nature Struct. Biol. 7, 602–608 (2000).

    Article  CAS  PubMed  Google Scholar 

  44. Chantalat, L. et al. Crystal structure of human survivin reveals a bow tie-shaped dimer with two unusual α-helical extensions. Mol. Cell 6, 183–189 (2000).

    Article  CAS  PubMed  Google Scholar 

  45. Sun, C., Nettesheim, D., Liu, Z. & Olejniczak, E. T. Solution structure of human survivin and its binding interface with Smac/Diablo. Biochemistry 44, 11–17 (2005).

    Article  CAS  PubMed  Google Scholar 

  46. Berezov, A. et al. Disabling the mitotic spindle and tumor growth by targeting a cavity-induced allosteric site of survivin. Oncogene 31, 1938–1948 (2012).

    Article  CAS  PubMed  Google Scholar 

  47. Wheatley, S. P., Henzing, A. J., Dodson, H., Khaled, W. & Earnshaw, W. C. Aurora-B phosphorylation in vitro identifies a residue of survivin that is essential for its localization and binding to inner centromere protein (INCENP) in vivo. J. Biol. Chem. 279, 5655–5660 (2004).

    Article  CAS  PubMed  Google Scholar 

  48. Wheatley, S. P. et al. Phosphorylation by Aurora-B negatively regulates survivin function during mitosis. Cell Cycle 6, 1220–1230 (2007).

    Article  CAS  PubMed  Google Scholar 

  49. O'Connor, D. S. et al. Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin. Proc. Natl Acad. Sci. USA 97, 13103–13107 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. O'Connor, D. S., Wall, N. R., Porter, A. C. & Altieri, D. C. A p34cdc2 survival checkpoint in cancer. Cancer Cell 2, 43–54 (2002).

    Article  CAS  PubMed  Google Scholar 

  51. Colnaghi, R. & Wheatley, S. P. Liaisons between survivin and Plk1 during cell division and cell death. J. Biol. Chem. 285, 22592–22604 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Chu, Y. et al. Aurora B kinase activation requires survivin priming phosphorylation by PLK1. J. Mol. Cell. Biol. 3, 260–267 (2011).

    Article  CAS  PubMed  Google Scholar 

  53. Barrett, R. M., Colnaghi, R. & Wheatley, S. P. Threonine 48 in the BIR domain of survivin is critical to its mitotic and anti-apoptotic activities and can be phosphorylated by CK2 in vitro. Cell Cycle 10, 538–548 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Grossman, D., Kim, P. J., Schechner, J. S. & Altieri, D. C. Inhibition of melanoma tumor growth in vivo by survivin targeting. Proc. Natl Acad. Sci. USA 98, 635–640 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Yan, H. et al. Induction of melanoma cell apoptosis and inhibition of tumor growth using a cell-permeable Survivin antagonist. Oncogene 25, 6968–6974 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Vong, Q. P., Cao, K., Li, H. Y., Iglesias, P. A. & Zheng, Y. Chromosome alignment and segregation regulated by ubiquitination of survivin. Science 310, 1499–1504 (2005).

    Article  CAS  PubMed  Google Scholar 

  57. Montpetit, B., Hazbun, T. R., Fields, S. & Hieter, P. Sumoylation of the budding yeast kinetochore protein Ndc10 is required for Ndc10 spindle localization and regulation of anaphase spindle elongation. J. Cell Biol. 174, 653–663 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Sampath, S. C. et al. The chromosomal passenger complex is required for chromatin-induced microtubule stabilization and spindle assembly. Cell 118, 187–202 (2004). First description of Dasra A and B as X. laevis chromatin-binding proteins required for spindle assembly.

    Article  CAS  PubMed  Google Scholar 

  59. Nakajima, Y. et al. Nbl1p: a Borealin/Dasra/CSC-1-like protein essential for Aurora/Ipl1 complex function and integrity in Saccharomyces cerevisiae. Mol. Biol. Cell 20, 1772–1784 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Bohnert, K. A., Chen, J.-S., Clifford, D. M., Vander Kooi, C. W. & Gould, K. L. A link between aurora kinase and Clp1/Cdc14 regulation uncovered by the identification of a fission yeast borealin-like protein. Mol. Biol. Cell 20, 3646–3659 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. 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). The first description of a fourth member of the CPC.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Gao, S. et al. Australin: a chromosomal passenger protein required specifically for Drosophila melanogaster male meiosis. J. Cell Biol. 180, 521–535 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Ma, A. C., Chung, M. I., Liang, R. & Leung, A. Y. The role of survivin2 in primitive hematopoiesis during zebrafish development. Leukemia 23, 712–720 (2009).

    Article  CAS  PubMed  Google Scholar 

  64. Fernandez-Miranda, G. et al. Genetic disruption of aurora B uncovers an essential role for aurora C during early mammalian development. Development 138, 2661–2672 (2011).

    Article  CAS  PubMed  Google Scholar 

  65. Niedzialkowska, E. et al. Molecular basis for phosphospecific recognition of histone H3 tails by Survivin paralogues at inner centromeres. Mol. Biol. Cell 23, 1457–1466 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Bourhis, E., Hymowitz, S. G. & Cochran, A. G. The mitotic regulator Survivin binds as a monomer to its functional interactor Borealin. J. Biol. Chem. 282, 35018–35023 (2007).

    Article  CAS  PubMed  Google Scholar 

  67. Capalbo, L. et al. The chromosomal passenger complex controls the function of ESCRT-III Snf7 proteins during cytokinesis. Open Biology 2, 120070 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Carlton, J. G., Caballe, A., Agromayor, M., Kloc, M. & Martin-Serrano, J. ESCRT-III governs the Aurora B-mediated abscission checkpoint through CHMP4C. Science 336, 220–225 (2012). References 67 and 68 show that the CPC is involved in the control of abscission by regulating the activity of ESCRT-III proteins.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Hayama, S. et al. Phosphorylation and activation of cell division cycle associated 8 by aurora kinase B plays a significant role in human lung carcinogenesis. Cancer Res. 67, 4113–4122 (2007).

    Article  CAS  PubMed  Google Scholar 

  70. Jelluma, N. et al. Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment. Cell 132, 233–246 (2008).

    Article  CAS  PubMed  Google Scholar 

  71. Kaur, H., Bekier, M. E. & Taylor, W. R. Regulation of Borealin by phosphorylation at serine 219. J. Cell. Biochem. 111, 1291–1298 (2010).

    Article  CAS  PubMed  Google Scholar 

  72. Date, D., Dreier, M. R., Borton, M. T., Bekier, M. E. & Taylor, W. R. Effects of phosphatase and proteasome inhibitors on Borealin phosphorylation and degradation. J. Biochem. 151, 361–369 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Tsukahara, T., Tanno, Y. & Watanabe, Y. Phosphorylation of the CPC by Cdk1 promotes chromosome bi-orientation. Nature 467, 719–723 (2010). Explores the role of CDK phosphorylation of CPC components in centromeric targeting of the complex and its role in chromosome bi-orientation.

    Article  CAS  PubMed  Google Scholar 

  74. Maciejowski, J. et al. Mps1 directs the assembly of Cdc20 inhibitory complexes during interphase and mitosis to control M phase timing and spindle checkpoint signaling. J. Cell Biol. 190, 89–100 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Klein, U. R., Haindl, M., Nigg, E. A. & Muller, S. RanBP2 and SENP3 function in a mitotic SUMO2/3 conjugation–deconjugation cycle on Borealin. Mol. Biol. Cell 20, 410–418 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Werner, A., Flotho, A. & Melchior, F. The RanBP2/RanGAP1*SUMO1/Ubc9 complex is a multisubunit SUMO E3 ligase. Mol. Cell 46, 287–298 (2012).

    Article  CAS  PubMed  Google Scholar 

  77. 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).

    Article  CAS  PubMed  Google Scholar 

  78. Sessa, F. et al. Mechanism of Aurora B activation by INCENP and inhibition by hesperadin. Mol. Cell 18, 379–391 (2005). Structural analysis of an Aurora B–IN box complex in the presence of the inhibitor Hesperadin provides support for a two-step model of Aurora B activation.

    Article  CAS  PubMed  Google Scholar 

  79. Kelly, A. E. et al. Chromosomal enrichment and activation of the Aurora B pathway are coupled to spatially regulate spindle assembly. Dev. Cell 12, 31–43 (2007). Shows that clustering of the CPC leads to Aurora B kinase activation and contributes to spindle assembly.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Wang, E., Ballister, E. R. & Lampson, M. A. Aurora B dynamics at centromeres create a diffusion-based phosphorylation gradient. J. Cell Biol. 194, 539–549 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Fuller, B. G. et al. Midzone activation of aurora B in anaphase produces an intracellular phosphorylation gradient. Nature 453, 1132–1136 (2008). Describes, using FRET sensors, an Aurora B phosphorylation gradient centred at the spindle midzone that is essential to provide spatial clues in late mitosis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Rosasco-Nitcher, S. E., Lan, W., Khorasanizadeh, S. & Stukenberg, P. T. Centromeric Aurora-B activation requires TD-60, microtubules, and substrate priming phosphorylation. Science 319, 469–472 (2008).

    Article  CAS  PubMed  Google Scholar 

  83. Tseng, B. S., Tan, L., Kapoor, T. M. & Funabiki, H. Dual detection of chromosomes and microtubules by the chromosomal passenger complex drives spindle assembly. Dev. Cell 18, 903–912 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Petsalaki, E., Akoumianaki, T., Black, E. J., Gillespie, D. A. & Zachos, G. Phosphorylation at serine 331 is required for Aurora B activation. J. Cell Biol. 195, 449–466 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Zachos, G. et al. Chk1 is required for spindle checkpoint function. Dev. Cell 12, 247–260 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Han, Z., Riefler, G. M., Saam, J. R., Mango, S. E. & Schumacher, J. M. The C. elegans Tousled-like kinase contributes to chromosome segregation as a substrate and regulator of the Aurora B kinase. Curr. Biol. 15, 894–904 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Yeh, C. H., Yang, H. J., Lee, I. J. & Wu, Y. C. Caenorhabditis elegans TLK-1 controls cytokinesis by localizing AIR-2/Aurora B to midzone microtubules. Biochem. Biophys. Res. Commun. 400, 187–193 (2010).

    Article  CAS  PubMed  Google Scholar 

  88. Sumara, I. et al. A Cul3-based E3 ligase removes Aurora B from mitotic chromosomes, regulating mitotic progression and completion of cytokinesis in human cells. Dev. Cell 12, 887–900 (2007).

    Article  CAS  PubMed  Google Scholar 

  89. Fernandez-Miranda, G. et al. SUMOylation modulates the function of Aurora-B kinase. J. Cell Sci. 123, 2823–2833 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Ban, R., Nishida, T. & Urano, T. Mitotic kinase Aurora-B is regulated by SUMO-2/3 conjugation/deconjugation during mitosis. Genes Cells 16, 652–669 (2011).

    Article  CAS  PubMed  Google Scholar 

  91. Stewart, S. & Fang, G. Destruction box-dependent degradation of aurora B is mediated by the anaphase-promoting complex/cyclosome and Cdh1. Cancer Res. 65, 8730–8735 (2005).

    Article  CAS  PubMed  Google Scholar 

  92. Nguyen, H. G., Chinnappan, D., Urano, T. & Ravid, K. Mechanism of Aurora-B degradation and its dependency on intact KEN and A-boxes: identification of an aneuploidy-promoting property. Mol. Cell. Biol. 25, 4977–4992 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Guimaraes, G. J., Dong, Y., McEwen, B. F. & Deluca, J. G. Kinetochore–microtubule attachment relies on the disordered N-terminal tail domain of Hec1. Curr. Biol. 18, 1778–1184 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Welburn, J. P. et al. Aurora B phosphorylates spatially distinct targets to differentially regulate the kinetochore–microtubule interface. Mol. Cell 38, 383–392 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Liu, D. et al. Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase. J. Cell Biol. 188, 809–820 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. DeLuca, K. F., Lens, S. M. & DeLuca, J. G. Temporal changes in Hec1 phosphorylation control kinetochore–microtubule attachment stability during mitosis. J. Cell Sci. 124, 622–634 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Salimian, K. J. et al. Feedback control in sensing chromosome biorientation by the Aurora B kinase. Curr. Biol. 21, 1158–1165 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Trinkle-Mulcahy, L. et al. Time-lapse imaging reveals dynamic relocalization of PP1γ throughout the mammalian cell cycle. Mol. Biol. Cell 14, 107–117 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Trinkle-Mulcahy, L. et al. Repo-Man recruits PP1γ to chromatin and is essential for cell viability. J. Cell Biol. 172, 679–692 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Vagnarelli, P. et al. Condensin and Repo-Man–PP1 co-operate in the regulation of chromosome architecture during mitosis. Nature Cell Biol. 8, 1133–1142 (2006).

    Article  CAS  PubMed  Google Scholar 

  101. Posch, M. et al. Sds22 regulates Aurora B activity and microtubule–kinetochore interactions at mitosis. J. Cell Biol. 191, 61–74 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Kim, Y., Holland, A. J., Lan, W. & Cleveland, D. W. Aurora kinases and protein phosphatase 1 mediate chromosome congression through regulation of CENP-E. Cell 142, 444–455 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Meadows, J. C. et al. Spindle checkpoint silencing requires association of PP1 to both Spc7 and kinesin-8 motors. Dev. Cell 20, 739–750 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Akiyoshi, B., Nelson, C. R., Ranish, J. A. & Biggins, S. Quantitative proteomic analysis of purified yeast kinetochores identifies a PP1 regulatory subunit. Genes Dev. 23, 2887–2899 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Foley, E. A., Maldonado, M. & Kapoor, T. M. Formation of stable attachments between kinetochores and microtubules depends on the B56-PP2A phosphatase. Nature Cell Biol. 13, 1265–1271 (2011).

    Article  CAS  PubMed  Google Scholar 

  106. 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). Suggests for the first time that spatial proximity regulated by centromere stretch regulates the activity of Aurora B in releasing kinetochore–microtubule interactions.

    Article  CAS  PubMed  Google Scholar 

  107. Maresca, T. J. & Salmon, E. D. Welcome to a new kind of tension: translating kinetochore mechanics into a wait-anaphase signal. J. Cell Sci. 123, 825–835 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Lampson, M. A. & Cheeseman, I. M. Sensing centromere tension: Aurora B and the regulation of kinetochore function. Trends Cell Biol. 21, 133–140 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Liu, D., Vader, G., Vromans, M. J., Lampson, M. A. & Lens, S. M. Sensing chromosome bi-orientation by spatial separation of aurora B kinase from kinetochore substrates. Science 323, 1350–1353 (2009). Demonstrates, using FRET sensors, distance-dependent Aurora B phosphorylation of kinetochore substrates and proposes that this can have a role in detecting tension and regulating microtubule attachments.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Uchida, K. S. et al. Kinetochore stretching inactivates the spindle assembly checkpoint. J. Cell Biol. 184, 383–390 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Li, Y. et al. A novel histone deacetylase pathway regulates mitosis by modulating Aurora B kinase activity. Genes Dev. 20, 2566–2579 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Zhang, K. et al. The Set1 methyltransferase opposes Ipl1 aurora kinase functions in chromosome segregation. Cell 122, 723–734 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Tan, L. & Kapoor, T. M. Examining the dynamics of chromosomal passenger complex (CPC)-dependent phosphorylation during cell division. Proc. Natl Acad. Sci. USA 108, 16675–16680 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Hayashi-Takanaka, Y., Yamagata, K., Nozaki, N. & Kimura, H. Visualizing histone modifications in living cells: spatiotemporal dynamics of H3 phosphorylation during interphase. J. Cell Biol. 187, 781–790 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Beardmore, V. A., Ahonen, L. J., Gorbsky, G. J. & Kallio, M. J. Survivin dynamics increases at centromeres during G2/M phase transition and is regulated by microtubule–attachment and Aurora B kinase activity. J. Cell Sci. 117, 4033–4042 (2004).

    Article  CAS  PubMed  Google Scholar 

  117. Monier, K., Mouradian, S. & Sullivan, K. F. DNA methylation promotes Aurora-B-driven phosphorylation of histone H3 in chromosomal subdomains. J. Cell Sci. 120, 101–114 (2007).

    Article  CAS  PubMed  Google Scholar 

  118. Kiyomitsu, T., Iwasaki, O., Obuse, C. & Yanagida, M. Inner centromere formation requires hMis14, a trident kinetochore protein that specifically recruits HP1 to human chromosomes. J. Cell Biol. 188, 791–807 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. 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).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  121. Fischle, W. et al. Regulation of HP1–chromatin binding by histone H3 methylation and phosphorylation. Nature 438, 1116–1122 (2005).

    Article  CAS  PubMed  Google Scholar 

  122. Hirota, T., Lipp, J. J., Toh, B. H. & Peters, J. M. Histone H3 serine 10 phosphorylation by Aurora B causes HP1 dissociation from heterochromatin. Nature 438, 1176–1180 (2005).

    Article  CAS  PubMed  Google Scholar 

  123. Bassett, E. A. et al. Epigenetic centromere specification directs aurora B accumulation but is insufficient to efficiently correct mitotic errors. J. Cell Biol. 190, 177–185 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Dai, J. & Higgins, J. M. Haspin: a mitotic histone kinase required for metaphase chromosome alignment. Cell Cycle 4, 665–668 (2005).

    Article  CAS  PubMed  Google Scholar 

  125. Kawashima, S. A. et al. Shugoshin enables tension-generating attachment of kinetochores by loading Aurora to centromeres. Genes Dev. 21, 420–435 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Polioudaki, H. et al. Mitotic phosphorylation of histone H3 at threonine 3. FEBS Lett. 560, 39–44 (2004).

    Article  CAS  PubMed  Google Scholar 

  127. Kawashima, S. A., Yamagishi, Y., Honda, T., Ishiguro, K. & Watanabe, Y. Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin. Science 327, 172–177 (2010).

    Article  CAS  PubMed  Google Scholar 

  128. Du, J., Kelly, A. E., Funabiki, H. & Patel, D. J. Structural basis for recognition of H3T3ph and Smac/DIABLO N-terminal peptides by human Survivin. Structure 20, 185–195 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Resnick, T. D. et al. INCENP and Aurora B promote meiotic sister chromatid cohesion through localization of the Shugoshin MEI-S332 in Drosophila. Dev. Cell 11, 57–68 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Aihara, H. et al. Nucleosomal histone kinase-1 phosphorylates H2A Thr 119 during mitosis in the early Drosophila embryo. Genes Dev. 18, 877–888 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Brittle, A. L., Nanba, Y., Ito, T. & Ohkura, H. Concerted action of Aurora B, Polo and NHK-1 kinases in centromere-specific histone 2A phosphorylation. Exp. Cell Res. 313, 2780–2785 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Wang, F. et al. A positive feedback loop involving Haspin and Aurora B promotes CPC accumulation at centromeres in mitosis. Curr. Biol. 21, 1061–1069 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Vigneron, S. et al. Kinetochore localization of spindle checkpoint proteins: who controls whom? Mol. Biol. Cell 15, 4584–4596 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Huang, H. et al. Tripin/hSgo2 recruits MCAK to the inner centromere to correct defective kinetochore attachments. J. Cell Biol. 177, 413–424 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Pouwels, J. et al. Shugoshin 1 plays a central role in kinetochore assembly and is required for kinetochore targeting of Plk1. Cell Cycle 6, 1579–1585 (2007).

    Article  CAS  PubMed  Google Scholar 

  136. Rivera, T. et al. Xenopus Shugoshin 2 regulates the spindle assembly pathway mediated by the chromosomal passenger complex. EMBO J. 31, 1467–1479 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. 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).

    Article  CAS  PubMed  Google Scholar 

  138. Losada, A., Yokochi, T. & Hirano, T. Functional contribution of Pds5 to cohesin-mediated cohesion in human cells and Xenopus egg extracts. J. Cell Sci. 118, 2133–2141 (2005).

    Article  CAS  PubMed  Google Scholar 

  139. Emanuele, M. J. et al. Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly. J. Cell Biol. 181, 241–254 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Xu, Z. et al. INCENP–aurora B interactions modulate kinase activity and chromosome passenger complex localization. J. Cell Biol. 187, 637–653 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Chang, C. J., Goulding, S., Adams, R. R., Earnshaw, W. C. & Carmena, M. Drosophila Incenp is required for cytokinesis and asymmetric cell division during development of the nervous system. J. Cell Sci. 119, 1144–1153 (2006).

    Article  CAS  PubMed  Google Scholar 

  143. Neurohr, G. et al. A midzone-based ruler adjusts chromosome compaction to anaphase spindle length. Science 332, 465–468 (2011).

    Article  CAS  PubMed  Google Scholar 

  144. 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, 669–682 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Ono, T., Fang, Y., Spector, D. L. & Hirano, T. Spatial and temporal regulation of condensins I and II in mitotic chromosome assembly in human cells. Mol. Biol. Cell 15, 3296–3308 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Lipp, J. J., Hirota, T., Poser, I. & Peters, J. M. Aurora B controls the association of condensin I but not condensin II with mitotic chromosomes. J. Cell Sci. 120, 1245–1255 (2007).

    Article  CAS  PubMed  Google Scholar 

  147. Collette, K. S., Petty, E. L., Golenberg, N., Bembenek, J. N. & Csankovszki, G. Different roles for Aurora B in condensin targeting during mitosis and meiosis. J. Cell Sci. 124, 3684–3694 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Nakazawa, N., Mehrotra, R., Ebe, M. & Yanagida, M. Condensin phosphorylated by the Aurora-B-like kinase Ark1 is continuously required until telophase in a mode distinct from Top2. J. Cell Sci. 124, 1795–1807 (2011).

    Article  CAS  PubMed  Google Scholar 

  149. Tada, K., Susumu, H., Sakuno, T. & Watanabe, Y. Condensin association with histone H2A shapes mitotic chromosomes. Nature 474, 477–483 (2011).

    Article  CAS  PubMed  Google Scholar 

  150. 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).

    Article  CAS  PubMed  Google Scholar 

  151. Nakazawa, N. et al. Dissection of the essential steps for condensin accumulation at kinetochores and rDNAs during fission yeast mitosis. J. Cell Biol. 180, 1115–1131 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Nicklas, R. B. & Koch, C. A. Chromosome micromanipulation. III. Spindle fiber tension and the reorientation of mal-oriented chromosomes. J. Cell Biol. 43, 40–50 (1969).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Lampson, M. A., Renduchitala, K., Khodjakov, A. & Kapoor, T. M. Correcting improper chromosome–spindle attachments during cell division. Nature Cell Biol. 6, 232–237 (2004). High-resolution microscopy reveals the role of chromosome and microtubule dynamics in the correction of spindle attachment errors by Aurora B.

    Article  CAS  PubMed  Google Scholar 

  155. Cimini, D., Wan, X., Hirel, C. B. & Salmon, E. D. Aurora kinase promotes turnover of kinetochore microtubules to reduce chromosome segregation errors. Curr. Biol. 16, 1711–1718 (2006).

    Article  CAS  PubMed  Google Scholar 

  156. Knowlton, A. L., Lan, W. & Stukenberg, P. T. Aurora B is enriched at merotelic attachment sites, where it regulates MCAK. Curr. Biol. 16, 1705–1710 (2006).

    Article  CAS  PubMed  Google Scholar 

  157. Powers, A. F. et al. The Ndc80 kinetochore complex forms load-bearing attachments to dynamic microtubule tips via biased diffusion. Cell 136, 865–875 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Deluca, J. G. et al. Kinetochore microtubule dynamics and attachment stability are regulated by Hec1. Cell 127, 969–982 (2006). Demonstration that Ndc80 is a crucial mediator of kinetochore–microtuble interactions that is negatively regulated by Aurora B.

    Article  CAS  PubMed  Google Scholar 

  159. Wei, R. R., Al-Bassam, J. & Harrison, S. C. The Ndc80/HEC1 complex is a contact point for kinetochore-microtubule attachment. Nature Struct. Mol. Biol. 14, 54–59 (2007).

    Article  CAS  Google Scholar 

  160. Ciferri, C. et al. Implications for kinetochore–microtubule attachment from the structure of an engineered Ndc80 complex. Cell 133, 427–339 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Miller, S. A., Johnson, M. L. & Stukenberg, P. T. Kinetochore attachments require an interaction between unstructured tails on microtubules and Ndc80(Hec1). Curr. Biol. 18, 1785–1791 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Tooley, J. G., Miller, S. A. & Stukenberg, P. T. The Ndc80 complex uses a tripartite attachment point to couple microtubule depolymerization to chromosome movement. Mol. Biol. Cell 22, 1217–1226 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Cheeseman, I. M., Chappie, J. S., Wilson-Kubalek, E. M. & Desai, A. The conserved KMN network constitutes the core microtubule-binding site of the kinetochore. Cell 127, 983–997 (2006). Identification of the conserved KMN network as a microtubule-binding module of the kinetochore negatively regulated by Aurora B.

    Article  CAS  PubMed  Google Scholar 

  164. Alushin, G. M. et al. The Ndc80 kinetochore complex forms oligomeric arrays along microtubules. Nature 467, 805–810 (2010). The way in which Ndc80 complexes bind to microtubules suggests a model for how Aurora B regulates kinetochore–microtubule attachments.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Hua, S. et al. CENP-U cooperates with Hec1 to orchestrate kinetochore–microtubule attachment. J. Biol. Chem. 286, 1627–1638 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  166. Gestaut, D. R. et al. Phosphoregulation and depolymerization-driven movement of the Dam1 complex do not require ring formation. Nature Cell Biol. 10, 407–414 (2008).

    Article  CAS  PubMed  Google Scholar 

  167. Cheeseman, I. M. et al. Phospho-regulation of kinetochore–microtubule attachments by the Aurora kinase Ipl1p. Cell 111, 163–172 (2002).

    Article  CAS  PubMed  Google Scholar 

  168. Tien, J. F. et al. Cooperation of the Dam1 and Ndc80 kinetochore complexes enhances microtubule coupling and is regulated by aurora B. J. Cell Biol. 189, 713–723 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Welburn, J. P. et al. The human kinetochore Ska1 complex facilitates microtubule depolymerization-coupled motility. Dev. Cell 16, 374–385 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Chan, Y. W., Jeyaprakash, A. A., Nigg, E. A. & Santamaria, A. Aurora B controls kinetochore–microtubule attachments by inhibiting Ska complex–KMN network interaction. J. Cell Biol. 196, 563–571 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Andrews, P. D. et al. Aurora B regulates MCAK at the mitotic centromere. Dev. Cell 6, 253–268 (2004).

    Article  CAS  PubMed  Google Scholar 

  172. Lan, W. et al. Aurora B phosphorylates centromeric MCAK and regulates its localization and microtubule depolymerization activity. Curr. Biol. 14, 273–286 (2004).

    Article  CAS  PubMed  Google Scholar 

  173. Ohi, R., Sapra, T., Howard, J. & Mitchison, T. J. Differentiation of cytoplasmic and meiotic spindle assembly MCAK functions by Aurora B-dependent phosphorylation. Mol. Biol. Cell 15, 2895–2906 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Tanno, Y. et al. Phosphorylation of mammalian Sgo2 by Aurora B recruits PP2A and MCAK to centromeres. Genes Dev. 24, 2169–2179 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Knowlton, A. L., Vorozhko, V. V., Lan, W., Gorbsky, G. J. & Stukenberg, P. T. ICIS and Aurora B coregulate the microtubule depolymerase Kif2a. Curr. Biol. 19, 758–763 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Tanenbaum, M. E. et al. A complex of Kif18b and MCAK promotes microtubule depolymerization and is negatively regulated by Aurora kinases. Curr. Biol. 21, 1356–1365 (2011).

    Article  CAS  PubMed  Google Scholar 

  177. Tanenbaum, M. E. & Medema, R. H. Localized Aurora B activity spatially controls non-kinetochore microtubules during spindle assembly. Chromosoma 120, 599–607 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Cheng, L. et al. Aurora B regulates formin mDia3 in achieving metaphase chromosome alignment. Dev. Cell 20, 342–352 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Pinsky, B. A., Kung, C., Shokat, K. M. & Biggins, S. The Ipl1–Aurora protein kinase activates the spindle checkpoint by creating unattached kinetochores. Nature Cell Biol. 8, 78–83 (2006). Demonstrates that budding yeast Aurora B supports SAC activation by generating unattached kinetochores.

    Article  CAS  PubMed  Google Scholar 

  181. Yang, Z., Kenny, A. E., Brito, D. A. & Rieder, C. L. Cells satisfy the mitotic checkpoint in Taxol, and do so faster in concentrations that stabilize syntelic attachments. J. Cell Biol. 186, 675–684 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. 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).

    Article  CAS  PubMed  Google Scholar 

  183. Vanoosthuyse, V. & Hardwick, K. G. A novel protein phosphatase 1-dependent spindle checkpoint silencing mechanism. Curr. Biol. 19, 1176–1181 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Famulski, J. K. & Chan, G. K. Aurora B kinase-dependent recruitment of hZW10 and hROD to tensionless kinetochores. Curr. Biol. 17, 2143–2149 (2007).

    Article  CAS  PubMed  Google Scholar 

  185. Saurin, A. T., van der Waal, M. S., Medema, R. H., Lens, S. M. & Kops, G. J. Aurora B potentiates Mps1 activation to ensure rapid checkpoint establishment at the onset of mitosis. Nature Commun. 2, 316 (2011).

    Article  CAS  Google Scholar 

  186. Santaguida, S., Vernieri, C., Villa, F., Ciliberto, A. & Musacchio, A. Evidence that Aurora B is implicated in spindle checkpoint signalling independently of error correction. EMBO J. 30, 1508–1519 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Maldonado, M. & Kapoor, T. M. Constitutive Mad1 targeting to kinetochores uncouples checkpoint signalling from chromosome biorientation. Nature Cell Biol. 13, 475–482 (2011).

    Article  CAS  PubMed  Google Scholar 

  188. Matson, D. R., Demirel, P. B., Stukenberg, P. T. & Burke, D. J. A conserved role for COMA/CENP-H/I/N kinetochore proteins in the spindle checkpoint. Genes Dev. 26, 542–547 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Rosenberg, J. S., Cross, F. R. & Funabiki, H. KNL1/Spc105 recruits PP1 to silence the spindle assembly checkpoint. Curr. Biol. 21, 942–947 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Espeut, J., Cheerambathur, D. K., Krenning, L., Oegema, K. & Desai, A. Microtubule binding by KNL-1 contributes to spindle checkpoint silencing at the kinetochore. J. Cell Biol. 196, 469–482 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Shepperd, L. A. et al. Phosphodependent recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 kinase maintains the spindle checkpoint. Curr. Biol. 22, 891–899 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  192. London, N., Ceto, S., Ranish, J. A. & Biggins, S. Phosphoregulation of Spc105 by Mps1 and PP1 regulates Bub1 localization to kinetochores. Curr. Biol. 22, 900–906 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Yamagishi, Y., Yang, C. H., Tanno, Y. & Watanabe, Y. MPS1/Mph1 phosphorylates the kinetochore protein KNL1/Spc7 to recruit SAC components. Nature Cell Biol. 14, 746–752 (2012).

    Article  CAS  PubMed  Google Scholar 

  194. Kasuboski, J. M. et al. Zwint-1 is a novel Aurora B substrate required for the assembly of a dynein-binding platform on kinetochores. Mol. Biol. Cell 22, 3318–3330 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Earnshaw, W. C. & Cooke, C. A. Analysis of the distribution of the INCENPs throughout mitosis reveals the existence of a pathway of structural changes in the chromosomes during metaphase and early events in cleavage furrow formation. J. Cell Sci. 98, 443–461 (1991).

    Article  PubMed  Google Scholar 

  196. Hummer, S. & Mayer, T. U. Cdk1 negatively regulates midzone localization of the mitotic kinesin mklp2 and the chromosomal passenger complex. Curr. Biol. 19, 607–612 (2009). Demonstration that Mklp2-driven localization of the CPC to the spindle midzone is negatively regulated by CDK phosphorylation.

    Article  PubMed  CAS  Google Scholar 

  197. Qian, J., Lesage, B., Beullens, M., Van Eynde, A. & Bollen, M. PP1/Repo-Man dephosphorylates mitotic histone H3 at T3 and regulates chromosomal Aurora B targeting. Curr. Biol. 21, 766–773 (2011).

    Article  CAS  PubMed  Google Scholar 

  198. Vagnarelli, P. et al. Repo-Man coordinates chromosomal reorganization with nuclear envelope reassembly during mitotic exit. Dev. Cell 21, 328–342 (2011).

    Article  CAS  PubMed  Google Scholar 

  199. Maerki, S. et al. The Cul3–KLHL21 E3 ubiquitin ligase targets aurora B to midzone microtubules in anaphase and is required for cytokinesis. J. Cell Biol. 187, 791–800 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Ramadan, K. et al. Cdc48/p97 promotes reformation of the nucleus by extracting the kinase Aurora B from chromatin. Nature 450, 1258–1262 (2007).

    Article  CAS  PubMed  Google Scholar 

  201. Dobrynin, G. et al. Cdc48/p97–Ufd1–Npl4 antagonizes Aurora B during chromosome segregation in HeLa cells. J. Cell Sci. 124, 1571–1180 (2011).

    Article  CAS  PubMed  Google Scholar 

  202. Gruneberg, U., Neef, R., Honda, R., Nigg, E. A. & Barr, F. A. Relocation of Aurora B from centromeres to the central spindle at the metaphase to anaphase transition requires MKlp2. J. Cell Biol. 166, 167–172 (2004). Mklp2 mediates targeting of the CPC to the central spindle.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Jang, J. K., Rahman, T. & McKim, K. S. The kinesinlike protein Subito contributes to central spindle assembly and organization of the meiotic spindle in Drosophila oocytes. Mol. Biol. Cell 16, 4684–4694 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Cesario, J. M. et al. Kinesin 6 family member Subito participates in mitotic spindle assembly and interacts with mitotic regulators. J. Cell Sci. 119, 4770–4780 (2006).

    Article  CAS  PubMed  Google Scholar 

  205. Chen, Q., Lakshmikanth, G. S., Spudich, J. A. & De Lozanne, A. The localization of inner centromeric protein (INCENP) at the cleavage furrow is dependent on Kif12 and involves interactions of the N terminus of INCENP with the actin cytoskeleton. Mol. Biol. Cell 18, 3366–3374 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  206. Zimniak, T. et al. Spatiotemporal regulation of Ipl1/Aurora activity by direct Cdk1 phosphorylation. Curr. Biol. 22, 787–793 (2012).

    Article  CAS  PubMed  Google Scholar 

  207. Coelho, P. A. et al. Dual role of topoisomerase II in centromere resolution and aurora B activity. PLoS Biol. 6, e207 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  208. Yang, F. et al. Identification of a novel mitotic phosphorylation motif associated with protein localization to the mitotic apparatus. J. Cell Sci. 120, 4060–4070 (2007).

    Article  CAS  PubMed  Google Scholar 

  209. Mollinari, C. et al. PRC1 is a microtubule binding and bundling protein essential to maintain the mitotic spindle midzone. J. Cell Biol. 157, 1175–1186 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Kurasawa, Y., Earnshaw, W. C., Mochizuki, Y., Dohmae, N. & Todokoro, K. Essential roles of KIF4 and its binding partner PRC1 in organized central spindle midzone formation. EMBO J. 23, 3237–3248 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  211. Mishima, M., Kaitna, S. & Glotzer, M. Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity. Dev. Cell 2, 41–54 (2002).

    Article  CAS  PubMed  Google Scholar 

  212. Kuriyama, R., Gustus, C., Terada, Y., Uetake, Y. & Matuliene, J. CHO1, a mammalian kinesin-like protein, interacts with F-actin and is involved in the terminal phase of cytokinesis. J. Cell Biol. 156, 783–790 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  213. Matuliene, J. & Kuriyama, R. Kinesin-like protein CHO1 is required for the formation of midbody matrix and the completion of cytokinesis in mammalian cells. Mol. Biol. Cell 13, 1832–1845 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  214. Douglas, M. E., Davies, T., Joseph, N. & Mishima, M. Aurora B and 14-3-3 coordinately regulate clustering of centralspindlin during cytokinesis. Curr. Biol. 20, 927–933 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Ozlü, N. et al. Binding partner switching on microtubules and aurora-B in the mitosis to cytokinesis transition. Mol. Cell. Proteom. 9, 336–350 (2010).

    Article  CAS  Google Scholar 

  216. Rappaport, R. Cytokinesis in animal cells. (eds Barlow, P.W., Bard, J.B.L., Greem, P.B. & Kirk, D.L.) (Cambridge Univ. Press, 1996).

    Book  Google Scholar 

  217. Fededa, J. P. & Gerlich, D. W. Molecular control of animal cell cytokinesis. Nature Cell Biol. 14, 440–447 (2012).

    Article  CAS  PubMed  Google Scholar 

  218. Eckley, D. M., Ainsztein, A. M., Mackay, A. M., Goldberg, I. G. & Earnshaw, W. C. Chromosomal proteins and cytokinesis: patterns of cleavage furrow formation and inner centromere protein positioning in mitotic heterokaryons and mid-anaphase cells. J. Cell Biol. 136, 1169–1183 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  219. Yuce, O., Piekny, A. & Glotzer, M. An. ECT2–centralspindlin complex regulates the localization and function of RhoA. J. Cell Biol. 170, 571–582 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  220. Nishimura, Y. & Yonemura, S. Centralspindlin regulates ECT2 and RhoA accumulation at the equatorial cortex during cytokinesis. J. Cell Sci. 119, 104–114 (2006).

    Article  CAS  PubMed  Google Scholar 

  221. Petronczki, M., Glotzer, M., Kraut, N. & Peters, J. M. Polo-like kinase 1 triggers the initiation of cytokinesis in human cells by promoting recruitment of the RhoGEF Ect2 to the central spindle. Dev. Cell 12, 713–725 (2007).

    Article  CAS  PubMed  Google Scholar 

  222. Su, K. C., Takaki, T. & Petronczki, M. Targeting of the RhoGEF Ect2 to the equatorial membrane controls cleavage furrow formation during cytokinesis. Dev. Cell 21, 1104–1115 (2011).

    Article  CAS  PubMed  Google Scholar 

  223. Minoshima, Y. et al. Phosphorylation by Aurora B converts MgcRacGAP to a RhoGAP during cytokinesis. Dev. Cell 4, 549–560 (2003).

    Article  CAS  PubMed  Google Scholar 

  224. Touré, A. et al. Phosphoregulation of MgcRacGAP in mitosis involves Aurora B and Cdk1 protein kinases and the PP2A phosphatase. FEBS Lett. 582, 1182–1188 (2008).

    Article  PubMed  CAS  Google Scholar 

  225. Piekny, A., Werner, M. & Glotzer, M. Cytokinesis: welcome to the Rho zone. Trends Cell Biol. 15, 651–658 (2005).

    Article  CAS  PubMed  Google Scholar 

  226. Canman, J. C. et al. Inhibition of Rac by the GAP activity of centralspindlin is essential for cytokinesis. Science 322, 1543–1546 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  227. Lewellyn, L., Carvalho, A., Desai, A., Maddox, A. S. & Oegema, K. The chromosomal passenger complex and centralspindlin independently contribute to contractile ring assembly. J. Cell Biol. 193, 155–169 (2011). Important analysis of the role of the CPC in the regulation of cytokinesis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  228. Birkenfeld, J. et al. GEF-H1 modulates localized RhoA activation during cytokinesis under the c ontrol of mitotic kinases. Dev. Cell 12, 699–712 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. 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).

    Article  CAS  Google Scholar 

  230. Sanders, S. L. & Field, C. M. Cell division. Septins in common? Curr. Biol. 4, 907–910 (1994).

    Article  CAS  PubMed  Google Scholar 

  231. Byers, B. & Goetsch, L. A highly ordered ring of membrane-associated filaments in budding yeast. J. Cell Biol. 69, 717–721 (1976).

    Article  CAS  PubMed  Google Scholar 

  232. Hartwell, L. H. Genetic control of the cell division cycle in yeast. IV. Genes controlling bud emergence and cytokinesis. Exp. Cell Res. 69, 265–276 (1971).

    Article  CAS  PubMed  Google Scholar 

  233. Neufeld, T. P. & Rubin, G. M. The Drosophila peanut gene is required for cytokinesis and encodes a protein similar to yeast putative bud neck filament proteins. Cell 77, 371–379 (1994).

    Article  CAS  PubMed  Google Scholar 

  234. Kinoshita, M. et al. Nedd5, a mammalian septin, is a novel cytoskeletal component interacting with actin-based structures. Genes Dev. 11, 1535–1547 (1997).

    Article  CAS  PubMed  Google Scholar 

  235. Gillis, A. N., Thomas, S., Hansen, S. D. & Kaplan, K. B. A novel role for the CBF3 kinetochore-scaffold complex in regulating septin dynamics and cytokinesis. J. Cell Biol. 171, 773–784 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  236. Thomas, S. & Kaplan, K. B. A. Bir1p Sli15p kinetochore passenger complex regulates septin organization during anaphase. Mol. Biol. Cell 18, 3820–3834 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  237. Qi, M. et al. Septin1, a new interaction partner for human serine/threonine kinase Aurora-B. Biochem. Biophys. Res. Commun. 336, 994–1000 (2005).

    Article  CAS  PubMed  Google Scholar 

  238. Wu, J. Q., Ye, Y., Wang, N., Pollard, T. D. & Pringle, J. R. Cooperation between the septins and the actomyosin ring and role of a cell-integrity pathway during cell division in fission yeast. Genetics 186, 897–915 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  239. Schonichen, A. et al. Biochemical characterization of the diaphanous autoregulatory interaction in the formin homology protein FHOD1. J. Biol. Chem. 281, 5084–5093 (2006).

    Article  PubMed  CAS  Google Scholar 

  240. Heald, R. & McKeon, F. Mutations of phosphorylation sites in lamin A that prevent nuclear lamina disassembly in mitosis. Cell 61, 579–589 (1990).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  242. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  243. Norden, C. et al. The NoCut pathway links completion of cytokinesis to spindle midzone function to prevent chromosome breakage. Cell 125, 85–98 (2006).

    Article  CAS  PubMed  Google Scholar 

  244. Steigemann, P. et al. Aurora B-mediated abscission checkpoint protects against tetraploidization. Cell 136, 473–484 (2009).

    Article  PubMed  CAS  Google Scholar 

  245. Mackay, D. R., Makise, M. & Ullman, K. S. Defects in nuclear pore assembly lead to activation of an Aurora B-mediated abscission checkpoint. J. Cell Biol. 191, 923–931 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  246. Dukes, J. D., Richardson, J. D., Simmons, R. & Whitley, P. A dominant-negative ESCRT-III protein perturbs cytokinesis and trafficking to lysosomes. Biochem. J. 411, 233–239 (2008).

    Article  CAS  PubMed  Google Scholar 

  247. Elia, N., Sougrat, R., Spurlin, T. A., Hurley, J. H. & Lippincott-Schwartz, J. Dynamics of endosomal sorting complex required for transport (ESCRT) machinery during cytokinesis and its role in abscission. Proc. Natl Acad. Sci. USA 108, 4846–4851 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  248. Guizetti, J. et al. Cortical constriction during abscission involves helices of ESCRT-III-dependent filaments. Science 331, 1616–1620 (2011).

    Article  CAS  PubMed  Google Scholar 

  249. Koch, A., Krug, K., Pengelley, S., Macek, B. & Hauf, S. Mitotic substrates of the kinase aurora with roles in chromatin regulation identified through quantitative phosphoproteomics of fission yeast. Sci. Signal. 4, rs6 (2011).

    Article  CAS  PubMed  Google Scholar 

  250. Wang, F. et al. Haspin inhibitors reveal centromeric functions of Aurora B in chromosome segregation. J. Cell Biol. 199, 251–268 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  251. De Antoni, A., Maffini, S., Knapp, S., Musacchio, A. & Santaguida, S. A small-molecule inhibitor of Haspin alters the kinetochore functions of Aurora B. J. Cell Biol. 199, 269–284 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

H.F. is supported by a US National Institutes of Health grant (R01GM075249). Work in the W.C.E. laboratory is funded by The Wellcome Trust (grant number 073915), of which W.C.E. is a Principal Research Fellow. The Wellcome Trust Centre for Cell Biology is supported by core grant numbers 077707 and 092076.

Author information

Author notes

  1. Mar Carmena and Michael Wheelock: These authors contributed equally to this work.

Authors and Affiliations

  1. Wellcome Trust Centre for Cell Biology, University of Edinburgh, ICB Michael Swann Building, King's Buildings Mayfield Road, Edinburgh, EH9 3JR, Scotland, UK

    Mar Carmena & William C. Earnshaw

  2. The Rockefeller University, 1230 York Ave, New York, 10065, New York, USA

    Michael Wheelock & Hironori Funabiki

Authors
  1. Mar Carmena
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Wheelock
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hironori Funabiki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. William C. Earnshaw
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Mar Carmena, Hironori Funabiki or William C. Earnshaw.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

William C. Earnshaw's homepage

Hironori Funabiki's homepage

Glossary

Spindle midzone

A region of the anaphase spindle that is composed of overlapping antiparallel microtubules from opposite spindle poles. It is also known as the central spindle.

Spindle assembly checkpoint

(SAC). The checkpoint that monitors chromosome attachment to the mitotic spindle and delays anaphase onset in response to unattached or tensionless kinetochores.

Guanine exchange factor

(GEF). Enzyme that activates small GTPases by stimulating the release of GDP and allowing the formation of the active GTP-bound form.

Kinetochores

Complex protein super-assemblies located at centromeres that mediate microtubule attachment and regulate chromosome segregation.

Baculovirus IAP repeat

(BIR). A Zn2+-coordinated globular domain that is involved in protein–protein interactions and is found in all inhibitor of apoptosis (IAP) proteins.

Centromere

Specialized chromatin at the primary constriction of mitotic chromosomes that is the site of kinetochore assembly and the focal point for sister chromatid cohesion.

Midbody

Dense structure that is derived from the remnants of the central spindle during late telophase. It is present in the intercellular bridge that connects daughter cells during cytokinesis.

Cyclin dependent kinases

(CDKs). A family of highly conserved Ser/Thr kinases that is involved in the regulation of cell cycle progression. CDKs are characterized by their association with and regulation by cyclins.

Polo-like kinases

(PLKs). Kinases first identified in Drosophila melanogaster that are involved in many aspects of cell cycle regulation, including chromosome–microtubule interactions and centrosome duplication.

Checkpoints

Biochemical signalling networks that monitor whether key processes have taken place before allowing progression to the next cell cycle stage.

Inner centromere

The region of the centromere that is located between paired sister chromatids.

Sumoylation

Post-translational modification by reversible conjugation of small ubiquitin-like modifier (SUMO) proteins. Sumoylated substrates are involved in regulation of the cell cycle, DNA repair, gene expression nuclear transport and protein stability.

E3 ligase

An enzyme that promotes the attachment of ubiquitin or small ubiquitin-like modifier (SUMO) to a protein. This leads to various outcomes, including changes in binding partners, sorting into different subcellular compartments or degradation.

FRET

(Förster resonance energy transfer). A method for the detection of associations between proteins by measuring the transfer of energy over distances of a few nanometres between fluorescent probes attached to the proteins.

KMN network

An important microtubule-binding module of the outer kinetochore that comprises the KNL1, Mis12 and Ndc80 complexes.

Condensin

A large heteropentameric complex that is essential for chromosome architecture. It is composed of two structural maintenance of chromosome (SMC) subunits and three auxiliary non-SMC subunits.

Kleisin

A subunit that bridges the ATPase heads of structural maintenance of chromosome (SMC) proteins in SMC complexes, thereby converting them into closed rings.

Merotelic attachments

A single kinetochore attaches to microtubules from both spindle poles.

Syntelic attachments

Both sister kinetochores attach to microtubules from the same pole.

Kinesin

A superfamily of microtubule associated motor proteins. Their functions include the transport of cargo along microtubules and the regulation of microtubule dynamics.

Formin

A protein that is defined by the presence of a catalytic FH2 (formin homology 2) domain. Formins interact with actin and regulate its polymerization.

AAA+ ATPase

Hexameric ATPases with associated and diverse cellular activities. They couple ATP hydrolysis to translocation or remodelling of macromolecules in several cellular processes.

DNA topoisomerase II

An abundant nuclear enzyme that relieves topological stress in DNA by passing one duplex through another using an ATP-regulated protein gate.

GTPase activating protein

(GAP). A protein that inactivates small GTPases by stimulating them to hydrolyze GTP into GDP.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carmena, M., Wheelock, M., Funabiki, H. et al. The chromosomal passenger complex (CPC): from easy rider to the godfather of mitosis. Nat Rev Mol Cell Biol 13, 789–803 (2012). https://doi.org/10.1038/nrm3474

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm3474

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