Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/49159
Title: ROLES OF B56 BOUND PROTEIN PHOSPHATASE 2A IN CHROMOSOME CONGRESSION REGULATION
Authors: XU PENG
Keywords: PP2A, Chromosome congression, BUBR1, MVA, Aurora B, HSET
Issue Date: 22-Aug-2013
Source: XU PENG (2013-08-22). ROLES OF B56 BOUND PROTEIN PHOSPHATASE 2A IN CHROMOSOME CONGRESSION REGULATION. ScholarBank@NUS Repository.
Abstract: Protein phosphatase 2A (PP2A) is one of the major serine/threonine phosphatases in regulating multiple cellular processes including mitosis. Here we observed that B56 family regulatory subunits of PP2A maintain chromosome stability by redundantly promoting chromosome congression. We identified BUBR1 as a novel B56 binding partner that explains the underlying mechanism. BUBR1 also promotes chromosome congression with the mechanism(s) remains elusive. We demonstrated that BUBR1 recruits B56 bound PP2A through direct interaction to facilitate kinetochore-microtubule (K-fiber) attachment and chromosome congression. Like BUBR1 depletion, point mutations in BUBR1 that block B56 binding also abolish chromosome congression and K-fiber formation, which can be reverted by Aurora B inhibition. Importantly, the failure of BUBR1 to recruit B56:PP2A is also directly responsible for chromosome congression defect found in cells from patients with the Mosaic Variegated Aneuploidy (MVA) syndrome caused by BUBR1 mutation. Strikingly, failure to recruit B56 to BUBR1 causes significant poleward chromosome accumulation. The poleward accumulation is regulated by minus-end-directed force on chromosomes, as depletion of minus-end-directed kinesin HSET/kinesin-14 can rescue this congression defect. We propose that B56:PP2A is a key mediator of BUBR1 for chromosome congression by antagonizing Aurora B activity at the kinetochore, leading to phosphorylation regulation of HSET that is essential for establishing stable K-fiber and congression.
URI: http://scholarbank.nus.edu.sg/handle/10635/49159
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