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BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression.

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Date
2013-05-15
Authors
Xu, Peng
Raetz, Elizabeth A
Kitagawa, Mayumi
Virshup, David M
Lee, Sang Hyun
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Abstract
BUBR1 is a mitotic phosphoprotein essential for the maintenance of chromosome stability by promoting chromosome congression and proper kinetochore-microtubule (K-fiber) attachment, but the underlying mechanism(s) has remained elusive. Here we identify BUBR1 as a binding partner of the B56 family of Protein Phosphatase 2A regulatory subunits. The interaction between BUBR1 and the B56 family is required for chromosome congression, since point mutations in BUBR1 that block B56 binding abolish chromosome congression. The BUBR1:B56-PP2A complex opposes Aurora B kinase activity, since loss of the complex can be reverted by inhibiting Aurora B. Importantly, we show that the failure of BUBR1 to recruit B56-PP2A also contributes to the chromosome congression defects found in cells derived from patients with the Mosaic Variegated Aneuploidy (MVA) syndrome. Together, we propose that B56-PP2A is a key mediator of BUBR1's role in chromosome congression and functions by antagonizing Aurora B activity at the kinetochore for establishing stable kinetochore-microtubule attachment at the metaphase plate.
Type
Journal article
Subject
Aurora B
B56-PP2A
BUBR1
Chromosome congression
Permalink
https://hdl.handle.net/10161/11681
Published Version (Please cite this version)
10.1242/bio.20134051
Publication Info
Xu, Peng; Raetz, Elizabeth A; Kitagawa, Mayumi; Virshup, David M; & Lee, Sang Hyun (2013). BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression. Biol Open, 2(5). pp. 479-486. 10.1242/bio.20134051. Retrieved from https://hdl.handle.net/10161/11681.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

David Marc Virshup

Professor of Pediatrics
Wnt Signaling and Cancer Biology; Circadian Rhythms; Pediatric Hematology/Oncology
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