Published online November 12, 2007
doi:10.1083/jcb.200708044
The Journal of Cell Biology, Vol. 179, No. 4, 611-617
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Wong et al.
Cdk1 phosphorylation of BubR1 controls spindle checkpoint arrest and Plk1-mediated formation of the 3F3/2 epitope
Oi Kwan Wong and
Guowei Fang
Department of Biological Sciences, Stanford University, Stanford, CA 94305
Correspondence to Guowei Fang: gwfang{at}stanford.edu
Accurate chromosome segregation is controlled by the spindle checkpoint, which senses kinetochore– microtubule attachments and tension across sister kinetochores. An important step in the tension-signaling pathway involves the phosphorylation of an unknown protein by polo-like kinase 1/Xenopus laevis polo-like kinase 1 (Plx1) on kinetochores lacking tension to generate the 3F3/2 phosphoepitope. We report here that the checkpoint protein BubR1 interacts with Plx1 and that phosphorylation of BubR1 by Plx1 generates the 3F3/2 epitope. Formation of the BubR1 3F3/2 epitope by Plx1 requires a prior phosphorylation of BubR1 on Thr 605 by cyclin-dependant kinase 1 (Cdk1). This priming phosphorylation of BubR1 by Cdk1 is required for checkpoint-mediated mitotic arrest and for recruitment of Plx1 and the checkpoint protein Mad2 to unattached kinetochores. Biochemically, formation of the 3F3/2 phosphoepitope by Cdk1 and Plx1 greatly enhances the kinase activity of BubR1. Thus, Cdk1-mediated phosphorylation of BubR1 controls checkpoint arrest and promotes the formation of the kinetochore 3F3/2 epitope.
O.K. Wong's present address is Sunesis Pharmaceuticals, South San Francisco, CA 94080.
Abbreviations used in this paper: APC/C, anaphase-promoting complex/cyclosome; CSF, cytostatic factor; KRB, kinase reaction buffer; Mps1, monopolar spindle 1; NEM, N-ethylmaleimide; PBD, polo box domain; Plk1, polo-like kinase 1; Plx1, Xenopus laevis polo-like kinase 1.
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