Skip to main content
SpringerLink
Log in

BUB1

  • Living reference work entry
  • First Online:
Encyclopedia of Signaling Molecules

  • 326 Accesses

Synonyms

BUB1L; BUB1A

Related Molecules in the Encyclopedia

MPS1; AURORA Kinases; BUBR1

Historical Background

Bub1 was originally discovered as a gene required for cell cycle arrest during mitosis in response to the microtubule depolymerizing drug benzimidazole in the model organism Saccharomyces cerevisiae (Hoyt et al. 1991). Mutant yeast were unable to arrest and inhibit the budding process at the end of mitosis, a marker for cell cycle progression, hence the name Budding Uninhibited by Benzimidazole 1 (BUB1). Through its capacity to contribute to mitotic arrest, BUB1 functions as an integral component of the spindle assembly checkpoint (SAC), a surveillance mechanism that delays mitotic progression until all kinetochores are properly attached to microtubules, and aligned at the spindle equator in metaphase. Since its original discovery in budding yeast, a SAC function for BUB1 has been verified in all model organisms studied to date (reviewed in (Elowe 2011). Soon after its...

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Asghar A, Lajeunesse A, Dulla K, Combes G, Thebault P, Nigg EA, et al. Bub1 autophosphorylation feeds back to regulate kinetochore docking and promote localized substrate phosphorylation. Nat Commun. 2015;6:8364. doi:10.1038/ncomms9364.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baron AP, von Schubert C, Cubizolles F, Siemeister G, Hitchcock M, Mengel A, et al. Probing the catalytic functions of Bub1 kinase using the small molecule inhibitors BAY-320 and BAY-524. Elife. 2016;5. doi:10.7554/eLife.12187.

    Google Scholar 

  • Basu J, Logarinho E, Herrmann S, Bousbaa H, Li Z, Chan GK, et al. Localization of the Drosophila checkpoint control protein Bub3 to the kinetochore requires Bub1 but not Zw10 or Rod. Chromosoma. 1998;107:376–85.

    Article  CAS  PubMed  Google Scholar 

  • Bernard P, Hardwick K, Javerzat JP. Fission yeast bub1 is a mitotic centromere protein essential for the spindle checkpoint and the preservation of correct ploidy through mitosis. J Cell Biol. 1998;143:1775–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bokros M, Gravenmier C, Jin F, Richmond D, Wang Y. Fin1-PP1 helps clear spindle assembly checkpoint protein Bub1 from kinetochores in anaphase. Cell Rep. 2016;14:1074–85. doi:10.1016/j.celrep.2016.01.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bolanos-Garcia VM, Blundell TL. BUB1 and BUBR1: multifaceted kinases of the cell cycle. Trends Biochem Sci. 2011;36:141–50. doi:10.1016/j.tibs.2010.08.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JK, Markowitz SD, et al. Mutations of mitotic checkpoint genes in human cancers. Nature. 1998;392:300–3. doi:10.1038/32688.

    Article  CAS  PubMed  Google Scholar 

  • Cahill DP, da Costa LT, Carson-Walter EB, Kinzler KW, Vogelstein B, Lengauer C. Characterization of MAD2B and other mitotic spindle checkpoint genes. Genomics. 1999;58:181–7. doi:10.1006/geno.1999.5831.

    Article  CAS  PubMed  Google Scholar 

  • Cheeseman IM. The kinetochore. Cold Spring Harb Perspect Biol. 2014;6:a015826. doi:10.1101/cshperspect.a015826.

    Article  PubMed  PubMed Central  Google Scholar 

  • Di Fiore B, Davey NE, Hagting A, Izawa D, Mansfeld J, Gibson TJ, et al. The ABBA motif binds APC/C activators and is shared by APC/C substrates and regulators. Dev Cell. 2015;32:358–72. doi:10.1016/j.devcel.2015.01.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elowe S. Bub1 and BubR1: at the interface between chromosome attachment and the spindle checkpoint. Mol Cell Biol. 2011;31:3085–93. doi:10.1128/MCB.05326-11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Encalada SE, Willis J, Lyczak R, Bowerman B. A spindle checkpoint functions during mitosis in the early Caenorhabditis elegans embryo. Mol Biol Cell. 2005;16:1056–70. doi:10.1091/mbc.E04-08-0712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Espert A, Uluocak P, Bastos RN, Mangat D, Graab P, Gruneberg U. PP2A-B56 opposes Mps1 phosphorylation of Knl1 and thereby promotes spindle assembly checkpoint silencing. J Cell Biol. 2014;206:833–42. doi:10.1083/jcb.201406109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Espeut J, Lara-Gonzalez P, Sassine M, Shiau AK, Desai A, Abrieu A. Natural loss of Mps1 kinase in nematodes uncovers a role for polo-like kinase 1 in spindle checkpoint initiation. Cell Rep. 2015;12:58–65. doi:10.1016/j.celrep.2015.05.039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fernius J, Hardwick KG. Bub1 kinase targets Sgo1 to ensure efficient chromosome biorientation in budding yeast mitosis. PLoS Genet. 2007;3:e213. doi:10.1371/journal.pgen.0030213.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gordon DJ, Resio B, Pellman D. Causes and consequences of aneuploidy in cancer. Nat Rev Genet. 2012;13:189–203. doi:10.1038/nrg3123.

    CAS  PubMed  Google Scholar 

  • Howell BJ, Moree B, Farrar EM, Stewart S, Fang G, Salmon ED. Spindle checkpoint protein dynamics at kinetochores in living cells. Curr Biol. 2004;14:953–64. doi:10.1016/j.cub.2004.05.053.

    Article  CAS  PubMed  Google Scholar 

  • Hoyt MA, Totis L, Roberts BT. S. cerevisiae genes required for cell cycle arrest in response to loss of microtubule function. Cell. 1991;66:507–17.

    Article  CAS  PubMed  Google Scholar 

  • Jia L, Li B, Yu H. The Bub1-Plk1 kinase complex promotes spindle checkpoint signalling through Cdc20 phosphorylation. Nat Commun. 2016;7:10818. doi:10.1038/ncomms10818.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson VL, Scott MI, Holt SV, Hussein D, Taylor SS. Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and Mad2, and chromosome congression. J Cell Sci. 2004;117:1577–89. doi:10.1242/jcs.01006.

    Article  CAS  PubMed  Google Scholar 

  • Kang J, Yang M, Li B, Qi W, Zhang C, Shokat KM, et al. Structure and substrate recruitment of the human spindle checkpoint kinase Bub1. Mol Cell. 2008;32:394–405. doi:10.1016/j.molcel.2008.09.017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kawashima SA, Yamagishi Y, Honda T, Ishiguro K, Watanabe Y. Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin. Science. 2010;327:172–7. doi:10.1126/science.1180189.

    Article  CAS  PubMed  Google Scholar 

  • Kim S, Sun H, Tomchick DR, Yu H, Luo X. Structure of human Mad1 C-terminal domain reveals its involvement in kinetochore targeting. Proc Natl Acad Sci USA. 2012;109:6549–54. doi:10.1073/pnas.1118210109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kitajima TS, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima SA, et al. Shugoshin collaborates with protein phosphatase 2A to protect cohesin. Nature. 2006;441:46–52. doi:10.1038/nature04663.

    Article  CAS  PubMed  Google Scholar 

  • Kiyomitsu T, Obuse C, Yanagida M. Human Blinkin/AF15q14 is required for chromosome alignment and the mitotic checkpoint through direct interaction with Bub1 and BubR1. Dev Cell. 2007;13:663–76. doi:10.1016/j.devcel.2007.09.005.

    Article  CAS  PubMed  Google Scholar 

  • Klebig C, Korinth D, Meraldi P. Bub1 regulates chromosome segregation in a kinetochore-independent manner. J Cell Biol. 2009;185:841–58. doi:10.1083/jcb.200902128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krenn V, Wehenkel A, Li X, Santaguida S, Musacchio A. Structural analysis reveals features of the spindle checkpoint kinase Bub1-kinetochore subunit Knl1 interaction. J Cell Biol. 2012;196:451–67. doi:10.1083/jcb.201110013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krenn V, Overlack K, Primorac I, van Gerwen S, Musacchio A. KI motifs of human Knl1 enhance assembly of comprehensive spindle checkpoint complexes around MELT repeats. Curr Biol. 2014;24:29–39. doi:10.1016/j.cub.2013.11.046.

    Article  CAS  PubMed  Google Scholar 

  • Lee S, Thebault P, Freschi L, Beaufils S, Blundell TL, Landry CR, et al. Characterization of spindle checkpoint kinase Mps1 reveals domain with functional and structural similarities to tetratricopeptide repeat motifs of Bub1 and BubR1 checkpoint kinases. J Biol Chem. 2012;287:5988–6001. doi:10.1074/jbc.M111.307355.

    Article  CAS  PubMed  Google Scholar 

  • Lin Z, Jia L, Tomchick DR, Luo X, Yu H. Substrate-specific activation of the mitotic kinase Bub1 through intramolecular autophosphorylation and kinetochore targeting. Structure. 2014;22:1616–27. doi:10.1016/j.str.2014.08.020.

    Article  CAS  PubMed  Google Scholar 

  • Lischetti T, Zhang G, Sedgwick GG, Bolanos-Garcia VM, Nilsson J. The internal Cdc20 binding site in BubR1 facilitates both spindle assembly checkpoint signalling and silencing. Nat Commun. 2014;5:5563. doi:10.1038/ncomms6563.

    Article  CAS  PubMed  Google Scholar 

  • Liu H, Jia L, Yu H. Phospho-H2A and cohesin specify distinct tension-regulated Sgo1 pools at kinetochores and inner centromeres. Curr Biol. 2013;23:1927–33. doi:10.1016/j.cub.2013.07.078.

    Article  CAS  PubMed  Google Scholar 

  • Logarinho E, Resende T, Torres C, Bousbaa H. The human spindle assembly checkpoint protein Bub3 is required for the establishment of efficient kinetochore-microtubule attachments. Mol Biol Cell. 2008;19:1798–813. doi:10.1091/mbc.E07-07-0633.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • London N, Ceto S, Ranish JA, Biggins S. Phosphoregulation of Spc105 by Mps1 and PP1 regulates Bub1 localization to kinetochores. Curr Biol. 2012;22:900–6. doi:10.1016/j.cub.2012.03.052.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nijenhuis W, Vallardi G, Teixeira A, Kops GJ, Saurin AT. Negative feedback at kinetochores underlies a responsive spindle checkpoint signal. Nat Cell Biol. 2014;16:1257–64. doi:10.1038/ncb3065.

    Article  CAS  PubMed  Google Scholar 

  • Nyati S, Schinske-Sebolt K, Pitchiaya S, Chekhovskiy K, Chator A, Chaudhry N, et al. The kinase activity of the Ser/Thr kinase BUB1 promotes TGF-beta signaling. Sci Signal. 2015;8:ra1. doi:10.1126/scisignal.2005379.

    Article  PubMed  PubMed Central  Google Scholar 

  • Overlack K, Primorac I, Vleugel M, Krenn V, Maffini S, Hoffmann I, et al. A molecular basis for the differential roles of Bub1 and BubR1 in the spindle assembly checkpoint. Elife. 2015;4:e05269. doi:10.7554/eLife.05269.

    Article  PubMed  PubMed Central  Google Scholar 

  • Perera D, Taylor SS. Sgo1 establishes the centromeric cohesion protection mechanism in G2 before subsequent Bub1-dependent recruitment in mitosis. J Cell Sci. 2010;123:653–9. doi:10.1242/jcs.059501.

    Article  CAS  PubMed  Google Scholar 

  • Primorac I, Weir JR, Chiroli E, Gross F, Hoffmann I, van Gerwen S, et al. Bub3 reads phosphorylated MELT repeats to promote spindle assembly checkpoint signaling. Elife. 2013;2:e01030. doi:10.7554/eLife.01030.

    Article  PubMed  PubMed Central  Google Scholar 

  • Qi W, Yu H. KEN-box-dependent degradation of the Bub1 spindle checkpoint kinase by the anaphase-promoting complex/cyclosome. J Biol Chem. 2007;282:3672–9. doi:10.1074/jbc.M609376200.

    Article  CAS  PubMed  Google Scholar 

  • Ricke RM, Jeganathan KB, van Deursen JM. Bub1 overexpression induces aneuploidy and tumor formation through Aurora B kinase hyperactivation. J Cell Biol. 2011;193:1049–64. doi:10.1083/jcb.201012035.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ricke RM, Jeganathan KB, Malureanu L, Harrison AM, van Deursen JM. Bub1 kinase activity drives error correction and mitotic checkpoint control but not tumor suppression. J Cell Biol. 2012;199:931–49. doi:10.1083/jcb.201205115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rischitor PE, May KM, Hardwick KG. Bub1 is a fission yeast kinetochore scaffold protein, and is sufficient to recruit other spindle checkpoint proteins to ectopic sites on chromosomes. PLoS One. 2007;2:e1342. doi:10.1371/journal.pone.0001342.

    Article  PubMed  PubMed Central  Google Scholar 

  • Roberts BT, Farr KA, Hoyt MA. The Saccharomyces cerevisiae checkpoint gene BUB1 encodes a novel protein kinase. Mol Cell Biol. 1994;14:8282–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rosenberg JS, Cross FR, Funabiki H. KNL1/Spc105 recruits PP1 to silence the spindle assembly checkpoint. Curr Biol. 2011;21:942–7. doi:10.1016/j.cub.2011.04.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schvartzman JM, Sotillo R, Benezra R. Mitotic chromosomal instability and cancer: mouse modelling of the human disease. Nat Rev Cancer. 2010;10:102–15. doi:10.1038/nrc2781.

    Article  CAS  PubMed  Google Scholar 

  • Shah JV, Botvinick E, Bonday Z, Furnari F, Berns M, Cleveland DW. Dynamics of centromere and kinetochore proteins; implications for checkpoint signaling and silencing. Curr Biol. 2004;14:942–52. doi:10.1016/j.cub.2004.05.046.

    CAS  PubMed  Google Scholar 

  • Sharp-Baker H, Chen RH. Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity. J Cell Biol. 2001;153:1239–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shepperd LA, Meadows JC, Sochaj AM, Lancaster TC, Zou J, Buttrick GJ, et al. Phosphodependent recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 kinase maintains the spindle checkpoint. Curr Biol. 2012;22:891–9. doi:10.1016/j.cub.2012.03.051.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silva PM, Reis RM, Bolanos-Garcia VM, Florindo C, Tavares AA, Bousbaa H. Dynein-dependent transport of spindle assembly checkpoint proteins off kinetochores toward spindle poles. FEBS Lett. 2014;588:3265–73. doi:10.1016/j.febslet.2014.07.011.

    Article  CAS  PubMed  Google Scholar 

  • Suijkerbuijk SJ, Vleugel M, Teixeira A, Kops GJ. Integration of kinase and phosphatase activities by BUBR1 ensures formation of stable kinetochore-microtubule attachments. Dev Cell. 2012;23:745–55. doi:10.1016/j.devcel.2012.09.005.

    Article  CAS  PubMed  Google Scholar 

  • Tang Z, Shu H, Oncel D, Chen S, Yu H. Phosphorylation of Cdc20 by Bub1 provides a catalytic mechanism for APC/C inhibition by the spindle checkpoint. Mol Cell. 2004;16:387–97. doi:10.1016/j.molcel.2004.09.031.

    Article  CAS  PubMed  Google Scholar 

  • Tang Z, Shu H, Qi W, Mahmood NA, Mumby MC, Yu H. PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation. Dev Cell. 2006;10:575–85. doi:10.1016/j.devcel.2006.03.010.

    Article  CAS  PubMed  Google Scholar 

  • Taylor SS, McKeon F. Kinetochore localization of murine Bub1 is required for normal mitotic timing and checkpoint response to spindle damage. Cell. 1997;89:727–35.

    Article  CAS  PubMed  Google Scholar 

  • Taylor SS, Ha E, McKeon F. The human homologue of Bub3 is required for kinetochore localization of Bub1 and a Mad3/Bub1-related protein kinase. J Cell Biol. 1998;142:1–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vanoosthuyse V, Hardwick KG. A novel protein phosphatase 1-dependent spindle checkpoint silencing mechanism. Curr Biol. 2009;19:1176–81. doi:10.1016/j.cub.2009.05.060.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vanoosthuyse V, Valsdottir R, Javerzat JP, Hardwick KG. Kinetochore targeting of fission yeast Mad and Bub proteins is essential for spindle checkpoint function but not for all chromosome segregation roles of Bub1p. Mol Cell Biol. 2004;24:9786–801. doi:10.1128/MCB.24.22.9786-9801.2004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vleugel M, Tromer E, Omerzu M, Groenewold V, Nijenhuis W, Snel B, et al. Arrayed BUB recruitment modules in the kinetochore scaffold KNL1 promote accurate chromosome segregation. J Cell Biol. 2013;203:943–55. doi:10.1083/jcb.201307016.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vleugel M, Hoek TA, Tromer E, Sliedrecht T, Groenewold V, Omerzu M, et al. Dissecting the roles of human BUB1 in the spindle assembly checkpoint. J Cell Sci. 2015;128:2975–82. doi:10.1242/jcs.169821.

    Article  CAS  PubMed  Google Scholar 

  • von Schubert C, Cubizolles F, Bracher JM, Sliedrecht T, Kops GJ, Nigg EA. Plk1 and Mps1 cooperatively regulate the spindle assembly checkpoint in human cells. Cell Rep. 2015;12:66–78. doi:10.1016/j.celrep.2015.06.007.

    Article  Google Scholar 

  • Wang Z, Katsaros D, Shen Y, Fu Y, Canuto EM, Benedetto C, et al. Biological and clinical significance of MAD2L1 and BUB1, genes frequently appearing in expression signatures for breast cancer prognosis. PLoS One. 2015;10:e0136246. doi:10.1371/journal.pone.0136246.

    Article  PubMed  PubMed Central  Google Scholar 

  • Weaver BA, Cleveland DW. Does aneuploidy cause cancer? Curr Opin Cell Biol. 2006;18:658–67. doi:10.1016/j.ceb.2006.10.002.

    Article  CAS  PubMed  Google Scholar 

  • Weiss A, Attisano L. The TGFbeta superfamily signaling pathway. Wiley Interdiscip Rev Dev Biol. 2013;2:47–63. doi:10.1002/wdev.86.

    Article  CAS  PubMed  Google Scholar 

  • Zhang G, Lischetti T, Hayward DG, Nilsson J. Distinct domains in Bub1 localize RZZ and BubR1 to kinetochores to regulate the checkpoint. Nat Commun. 2015;6:7162. doi:10.1038/ncomms8162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre de recherche du CHUM, (Notre-Dame) et Institut du Cancer de Montréal, 900 rue St-Denis, Tour Viger Montréal, Québec, H2X0A9, Canada

    Adeel Asghar

  2. Axe of Reproduction, Mother and Youth Health, Centre de recherche du Centre Hospitalier Universitaire de Québec, Québec, QC, Canada

    Sabine Elowe

  3. The Department of Pediatrics, Faculty of Medicine, Université Laval, Québec City, G1V 4G2, QC, Canada

    Sabine Elowe

Authors
  1. Adeel Asghar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sabine Elowe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sabine Elowe .

Editor information

Editors and Affiliations

  1. Dept. Biological Science, Department of Molecular Science and Tech College of Natural Science, Suwon, Korea (Republic of)

    Sangdun Choi

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media LLC

About this entry

Cite this entry

Asghar, A., Elowe, S. (2016). BUB1. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_101546-1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-6438-9_101546-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-6438-9

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation