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.
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12 September 2005
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September 06 2005
Microtubule capture by CENP-E silences BubR1-dependent mitotic checkpoint signaling
Yinghui Mao,
Yinghui Mao
1Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093
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Arshad Desai,
Arshad Desai
1Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093
2Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093
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Don W. Cleveland
Don W. Cleveland
1Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093
2Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093
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Yinghui Mao
1Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093
Arshad Desai
1Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093
2Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093
Don W. Cleveland
1Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093
2Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093
Correspondence to Don W. Cleveland: [email protected]
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.
Received:
May 06 2005
Accepted:
August 05 2005
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2005
J Cell Biol (2005) 170 (6): 873–880.
Article history
Received:
May 06 2005
Accepted:
August 05 2005
Citation
Yinghui Mao, Arshad Desai, Don W. Cleveland; Microtubule capture by CENP-E silences BubR1-dependent mitotic checkpoint signaling . J Cell Biol 12 September 2005; 170 (6): 873–880. doi: https://doi.org/10.1083/jcb.200505040
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