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Microtubule capture by CENP-E silences BubR1-dependent mitotic checkpoint signaling

J. Cell Biol., 12 September 2005
Vol. 170, Issue 6, p. 873-880
DOI: 10.1083/jcb.200505040

Microtubule capture by CENP-E silences BubR1-dependent mitotic checkpoint signaling

  1. Yinghui Mao 1 ,
  2. Arshad Desai 1 , 2 , and
  3. Don W. Cleveland 1 , 2
  1. 1Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093
  2. 2Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093
  1. Correspondence to Don W. Cleveland: dcleveland{at}


The mitotic checkpoint is the major cell cycle control mechanism for maintaining chromosome content in multicellular organisms. Prevention of premature onset of anaphase requires activation at unattached kinetochores of the BubR1 kinase, which acts with other components to generate a diffusible “stop anaphase” inhibitor. Not only does direct binding of BubR1 to the centromere-associated kinesin family member CENP-E activate its essential kinase, binding of a motorless fragment of CENP-E is shown here to constitutively activate BubR1 bound at kinetochores, producing checkpoint signaling that is not silenced either by spindle microtubule capture or the tension developed at those kinetochores by other components. Using purified BubR1, microtubules, and CENP-E, microtubule capture by the CENP-E motor domain is shown to silence BubR1 kinase activity in a ternary complex of BubR1–CENP-E–microtubule. Together, this reveals that CENP-E is the signal transducing linker responsible for silencing BubR1-dependent mitotic checkpoint signaling through its capture at kinetochores of spindle microtubules.


  • Y. Mao's present address is Department of Pathology, Columbia University College of Physicians and Surgeons, New York, NY 10032.

  • Abbreviations used in this paper: APC/C, anaphase-promoting complex/cyclosome; CSF, cytostatic factor.

    • Submitted: 6 May 2005
    • Accepted: 5 August 2005


Y. Mao, A. Desai, and D. W. Cleveland, Microtubule capture by CENP-E silences BubR1-dependent mitotic checkpoint signaling. J. Cell Biol. 170, 873-880 (2005).

Preventing farnesylation of the dynein adaptor Spindly contributes to the mitotic defects caused by farnesyltransferase inhibitors
A. J. Holland, R. M. Reis, S. Niessen, C. Pereira, D. A. Andres, H. P. Spielmann, D. W. Cleveland, A. Desai, and R. Gassmann
Mol. Biol. Cell 26, 1845-1856 (15 May 2015)

Cenp-meta is required for sustained spindle checkpoint
T. Rubin, R. E. Karess, and Z. Rahmani
Biology Open 3, 522-528 (15 June 2014)

Cancer-Specific Requirement for BUB1B/BUBR1 in Human Brain Tumor Isolates and Genetically Transformed Cells
Y. Ding, C. G. Hubert, J. Herman, P. Corrin, C. M. Toledo, K. Skutt-Kakaria, J. Vazquez, R. Basom, B. Zhang, J. K. Risler et al.
Cancer Discovery 3, 198-211 (1 February 2013)

Force generation by kinesin and myosin cytoskeletal motor proteins
F. J. Kull, and S. A. Endow
J. Cell Sci. 126, 9-19 (1 January 2013)

CENP-E-dependent BubR1 autophosphorylation enhances chromosome alignment and the mitotic checkpoint
Y. Guo, C. Kim, S. Ahmad, J. Zhang, and Y. Mao
JCB 198, 205-217 (23 July 2012)

Gene expression profiles in promoted-growth rice seedlings that germinated from the seeds implanted by low-energy N+ beam
H. Ya, Q. Chen, W. Wang, W. Chen, G. Qin, and Z. Jiao
J Radiat Res 53, 558-569 (1 July 2012)

CENP-E Kinesin Interacts with SKAP Protein to Orchestrate Accurate Chromosome Segregation in Mitosis
Y. Huang, W. Wang, P. Yao, X. Wang, X. Liu, X. Zhuang, F. Yan, J. Zhou, J. Du, T. Ward et al.
J Biol Chem 287, 1500-1509 (6 January 2012)

Bub1 and BubR1: at the Interface between Chromosome Attachment and the Spindle Checkpoint
S. Elowe, W. Wang, P. Yao, X. Wang, X. Liu, X. Zhuang, F. Yan, J. Zhou, J. Du, T. Ward et al.
Mol. Cell. Biol. 31, 3085-3093 (1 August 2011)

Defining the Molecular Basis of BubR1 Kinetochore Interactions and APC/C-CDC20 Inhibition
S. D'Arcy, O. R. Davies, T. L. Blundell, and V. M. Bolanos-Garcia
J Biol Chem 285, 14764-14776 (7 May 2010)

Antitumor activity of an allosteric inhibitor of centromere-associated protein-E
K. W. Wood, L. Lad, L. Luo, X. Qian, S. D. Knight, N. Nevins, K. Brejc, D. Sutton, A. G. Gilmartin, P. R. Chua et al.
Proc. Natl. Acad. Sci. USA 107, 5839-5844 (30 March 2010)

Targeting a kinetochore-associated motor protein to kill cancer cells
S. A. Wacker, and T. M. Kapoor
Proc. Natl. Acad. Sci. USA 107, 5699-5700 (30 March 2010)

Overcoming inhibition in the spindle checkpoint
V. Vanoosthuyse, and K. G. Hardwick
Genes Dev. 23, 2799-2805 (15 December 2009)

Identification of FANCA as a protein interacting with centromere-associated protein E
J. Du, L. Chen, and J. Shen
Acta Biochim Biophys Sin 41, 816-821 (1 October 2009)

PinX1 Is a Novel Microtubule-binding Protein Essential for Accurate Chromosome Segregation
K. Yuan, N. Li, K. Jiang, T. Zhu, Y. Huo, C. Wang, J. Lu, A. Shaw, K. Thomas, J. Zhang et al.
J Biol Chem 284, 23072-23082 (21 August 2009)

G2 histone methylation is required for the proper segregation of chromosomes
R. Heit, J. B. Rattner, G. K. T. Chan, and M. J. Hendzel
J. Cell Sci. 122, 2957-2968 (15 August 2009)

Understanding the role of aneuploidy in tumorigenesis
J. H. Bannon, and M. M. Mc Gee
Biochm. Soc. Trans. 37, 910-913 (1 August 2009)

BubR1 acetylation at prometaphase is required for modulating APC/C activity and timing of mitosis
E. Choi, H. Choe, J. Min, J. Y. Choi, J. Kim, and H. Lee
EMBO J. 28, 2077-2089 (22 July 2009)

Kinase Signaling in the Spindle Checkpoint
J. Kang, and H. Yu
J Biol Chem 284, 15359-15363 (5 June 2009)

Systematic Analysis in Caenorhabditis elegans Reveals that the Spindle Checkpoint Is Composed of Two Largely Independent Branches
A. Essex, A. Dammermann, L. Lewellyn, K. Oegema, and A. Desai
Mol. Biol. Cell 20, 1252-1267 (1 February 2009)

UA62784, a novel inhibitor of centromere protein E kinesin-like protein
M. C. Henderson, Y.-J. Y. Shaw, H. Wang, H. Han, L. H. Hurley, G. Flynn, R. T. Dorr, and D. D. Von Hoff
Molecular Cancer Therapeutics 8, 36-44 (1 January 2009)

Centromere-Associated Protein E: A Motor That Puts the Brakes on the Mitotic Checkpoint
K. W. Wood, P. Chua, D. Sutton, and J. R. Jackson
Clin. Cancer Res. 14, 7588-7592 (1 December 2008)

Phosphorylation sites in BubR1 that regulate kinetochore attachment, tension, and mitotic exit
H. Huang, J. Hittle, F. Zappacosta, R. S. Annan, A. Hershko, and T. J. Yen
JCB 183, 667-680 (17 November 2008)

Septin 7 Interacts with Centromere-associated Protein E and Is Required for Its Kinetochore Localization
M. Zhu, F. Wang, F. Yan, P. Y. Yao, J. Du, X. Gao, X. Wang, Q. Wu, T. Ward, J. Li et al.
J Biol Chem 283, 18916-18925 (4 July 2008)

The mitotic kinesin CENP-E is a processive transport motor
H. Yardimci, M. van Duffelen, Y. Mao, S. S. Rosenfeld, and P. R. Selvin
Proc. Natl. Acad. Sci. USA 105, 6016-6021 (22 April 2008)

Bub1 mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis
K. Jeganathan, L. Malureanu, D. J. Baker, S. C. Abraham, and J. M. van Deursen
JCB 179, 255-267 (22 October 2007)

BubR1 and APC/EB1 cooperate to maintain metaphase chromosome alignment
J. Zhang, S. Ahmad, and Y. Mao
JCB 178, 773-784 (27 August 2007)

Spindly, a novel protein essential for silencing the spindle assembly checkpoint, recruits dynein to the kinetochore
E. R. Griffis, N. Stuurman, and R. D. Vale
JCB 177, 1005-1015 (30 July 2007)

Human NUF2 Interacts with Centromere-associated Protein E and Is Essential for a Stable Spindle Microtubule-Kinetochore Attachment
D. Liu, X. Ding, J. Du, X. Cai, Y. Huang, T. Ward, A. Shaw, Y. Yang, R. Hu, C. Jin et al.
J Biol Chem 282, 21415-21424 (20 July 2007)

Mitotic Chromosome Biorientation in Fission Yeast Is Enhanced by Dynein and a Minus-end-directed, Kinesin-like Protein
E. L. Grishchuk, I. S. Spiridonov, and J. R. McIntosh
Mol. Biol. Cell 18, 2216-2225 (1 June 2007)

Farnesyl transferase inhibitors impair chromosomal maintenance in cell lines and human tumors by compromising CENP-E and CENP-F function
K. Schafer-Hales, J. Iaconelli, J. P. Snyder, A. Prussia, J. H. Nettles, A. El-Naggar, F. R. Khuri, P. Giannakakou, and A. I. Marcus
Molecular Cancer Therapeutics 6, 1317-1328 (1 April 2007)

Loading of the 3F3/2 Antigen onto Kinetochores Is Dependent on the Ordered Assembly of the Spindle Checkpoint Proteins
O. K. Wong, and G. Fang
Mol. Biol. Cell 17, 4390-4399 (1 October 2006)

CELL BIOLOGY: Serving Up a Plate of Chromosomes
R. Heald, and G. Fang
Science 311, 343-344 (20 January 2006)

Chromosomes Can Congress to the Metaphase Plate Before Biorientation
T. M. Kapoor, M. A. Lampson, P. Hergert, L. Cameron, D. Cimini, E. D. Salmon, B. F. McEwen, and A. Khodjakov
Science 311, 388-391 (20 January 2006)

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