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XB-ART-4999
Cell July 11, 2003; 114 (1): 87-98.

Activating and silencing the mitotic checkpoint through CENP-E-dependent activation/inactivation of BubR1.

Mao Y , Abrieu A , Cleveland DW .


Abstract
The mitotic checkpoint prevents advance to anaphase prior to successful attachment of every centromere/kinetochore to mitotic spindle microtubules. Using purified components and Xenopus egg extracts, the kinetochore-associated microtubule motor CENP-E is now shown to be the activator of the essential checkpoint kinase BubR1. Since kinase activity and the checkpoint are silenced following CENP-E-dependent microtubule attachment in extracts or binding of CENP-E antibodies that do not disrupt CENP-E association with BubR1, CENP-E mediates silencing of BubR1 signaling. Checkpoint signaling requires the normal level of BubR1 containing a functional Mad3 domain implicated in Cdc20 binding, but only a small fraction need be kinase competent. This supports bifunctional roles for BubR1 in the checkpoint: an enzymatic one requiring CENP-E-dependent activation of its kinase activity at kinetochores and a stoichiometric one as a direct inhibitor of Cdc20.

PubMed ID: 12859900
Article link: Cell
Grant support: [+]
Genes referenced: bub1b cdc20 cenpe mxd3



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