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BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654266/ https://www.ncbi.nlm.nih.gov/pubmed/23789096 http://dx.doi.org/10.1242/bio.20134051 |
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author | Xu, Peng Raetz, Elizabeth A. Kitagawa, Mayumi Virshup, David M. Lee, Sang Hyun |
author_facet | Xu, Peng Raetz, Elizabeth A. Kitagawa, Mayumi Virshup, David M. Lee, Sang Hyun |
author_sort | Xu, Peng |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3654266 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Company of Biologists |
record_format | MEDLINE/PubMed |
spelling | pubmed-36542662013-06-20 BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression Xu, Peng Raetz, Elizabeth A. Kitagawa, Mayumi Virshup, David M. Lee, Sang Hyun Biol Open Research Article 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. The Company of Biologists 2013-03-25 /pmc/articles/PMC3654266/ /pubmed/23789096 http://dx.doi.org/10.1242/bio.20134051 Text en © 2013. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by-nc-sa/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Article Xu, Peng Raetz, Elizabeth A. Kitagawa, Mayumi Virshup, David M. Lee, Sang Hyun BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression |
title | BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression |
title_full | BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression |
title_fullStr | BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression |
title_full_unstemmed | BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression |
title_short | BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression |
title_sort | bubr1 recruits pp2a via the b56 family of targeting subunits to promote chromosome congression |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654266/ https://www.ncbi.nlm.nih.gov/pubmed/23789096 http://dx.doi.org/10.1242/bio.20134051 |
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