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Dev Cell. 2012 Oct 16;23(4):745-55. doi: 10.1016/j.devcel.2012.09.005.

Integration of kinase and phosphatase activities by BUBR1 ensures formation of stable kinetochore-microtubule attachments.

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1
Molecular Cancer Research and Cancer Genomics Centre, UMC Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.

Abstract

Maintenance of chromosomal stability depends on error-free chromosome segregation. The pseudokinase BUBR1 is essential for this, because it is a core component of the mitotic checkpoint and is required for formation of stable kinetochore-microtubule attachments. We have identified a conserved and highly phosphorylated domain (KARD) in BUBR1 that is crucial for formation of kinetochore-microtubule attachments. Deletion of this domain or prevention of its phosphorylation abolishes formation of kinetochore microtubules, which can be reverted by inhibiting Aurora B activity. Phosphorylation of KARD by PLK1 promotes direct interaction of BUBR1 with the PP2A-B56α phosphatase that counters excessive Aurora B activity at kinetochores. As a result, removal of BUBR1 from mitotic cells or inhibition of PLK1 reduces PP2A-B56α kinetochore binding and elevates phosphorylation of Aurora B substrates on the outer kinetochore. We propose that PLK1 and BUBR1 cooperate to stabilize kinetochore-microtubule interactions by regulating PP2A-B56α-mediated dephosphorylation of Aurora B substrates at the kinetochore-microtubule interface.

PMID:
23079597
DOI:
10.1016/j.devcel.2012.09.005
[Indexed for MEDLINE]
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