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J. Cell Biol. 170 (6): 873-880

Copyright © 2005 by the Rockefeller University Press.


Report

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

Yinghui Mao1, Arshad Desai1,2, , and Don W. Cleveland1,2

1 Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093
2 Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093

Correspondence to Don W. Cleveland: dcleveland{at}ucsd.edu

Abstract Back to Top

Abstract: 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.


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