期刊
BIOLOGY OPEN
卷 2, 期 5, 页码 479-486出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/bio.20134051
关键词
Aurora B; B56-PP2A; BUBR1; Chromosome congression
类别
资金
- National Research Foundation of Singapore under its STAR
- National Research Fellow programs
- Duke-NUS Graduate Medical School
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. (C) 2013. Published by The Company of Biologists Ltd.
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