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Shugoshin-1 Balances Aurora B Kinase Activity via PP2A to Promote Chromosome Bi-orientation

Correction of faulty kinetochore-microtubule attachments is essential for faithful chromosome segregation and dictated by the opposing activities of Aurora B kinase and PP1 and PP2A phosphatases. How kinase and phosphatase activities are appropriately balanced is less clear. Here, we show that a cen...

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Autores principales: Meppelink, Amanda, Kabeche, Lilian, Vromans, Martijn J.M., Compton, Duane A., Lens, Susanne M.A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718550/
https://www.ncbi.nlm.nih.gov/pubmed/25892238
http://dx.doi.org/10.1016/j.celrep.2015.03.052
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author Meppelink, Amanda
Kabeche, Lilian
Vromans, Martijn J.M.
Compton, Duane A.
Lens, Susanne M.A.
author_facet Meppelink, Amanda
Kabeche, Lilian
Vromans, Martijn J.M.
Compton, Duane A.
Lens, Susanne M.A.
author_sort Meppelink, Amanda
collection PubMed
description Correction of faulty kinetochore-microtubule attachments is essential for faithful chromosome segregation and dictated by the opposing activities of Aurora B kinase and PP1 and PP2A phosphatases. How kinase and phosphatase activities are appropriately balanced is less clear. Here, we show that a centromeric pool of PP2A-B56 counteracts Aurora B T-loop phosphorylation and is recruited to centromeres through Shugoshin-1 (Sgo1). In non-transformed RPE-1 cells, Aurora B, Sgo1, and PP2A-B56 are enriched on centromeres and levels diminish as chromosomes establish bi-oriented attachments. Elevating Sgo1 levels at centromeres recruits excess PP2A-B56, and this counteracts Aurora B kinase activity, undermining efficient correction of kinetochore-microtubule attachment errors. Conversely, Sgo1-depleted cells display reduced centromeric localization of Aurora B, whereas the remaining kinase is hyperactive due to concomitant reduction of centromeric PP2A-B56. Our data suggest that Sgo1 can tune the stability of kinetochore-microtubule attachments through recruitment of PP2A-B56 that balances Aurora B activity at the centromere.
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spelling pubmed-47185502016-01-19 Shugoshin-1 Balances Aurora B Kinase Activity via PP2A to Promote Chromosome Bi-orientation Meppelink, Amanda Kabeche, Lilian Vromans, Martijn J.M. Compton, Duane A. Lens, Susanne M.A. Cell Rep Article Correction of faulty kinetochore-microtubule attachments is essential for faithful chromosome segregation and dictated by the opposing activities of Aurora B kinase and PP1 and PP2A phosphatases. How kinase and phosphatase activities are appropriately balanced is less clear. Here, we show that a centromeric pool of PP2A-B56 counteracts Aurora B T-loop phosphorylation and is recruited to centromeres through Shugoshin-1 (Sgo1). In non-transformed RPE-1 cells, Aurora B, Sgo1, and PP2A-B56 are enriched on centromeres and levels diminish as chromosomes establish bi-oriented attachments. Elevating Sgo1 levels at centromeres recruits excess PP2A-B56, and this counteracts Aurora B kinase activity, undermining efficient correction of kinetochore-microtubule attachment errors. Conversely, Sgo1-depleted cells display reduced centromeric localization of Aurora B, whereas the remaining kinase is hyperactive due to concomitant reduction of centromeric PP2A-B56. Our data suggest that Sgo1 can tune the stability of kinetochore-microtubule attachments through recruitment of PP2A-B56 that balances Aurora B activity at the centromere. 2015-04-16 2015-04-28 /pmc/articles/PMC4718550/ /pubmed/25892238 http://dx.doi.org/10.1016/j.celrep.2015.03.052 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Meppelink, Amanda
Kabeche, Lilian
Vromans, Martijn J.M.
Compton, Duane A.
Lens, Susanne M.A.
Shugoshin-1 Balances Aurora B Kinase Activity via PP2A to Promote Chromosome Bi-orientation
title Shugoshin-1 Balances Aurora B Kinase Activity via PP2A to Promote Chromosome Bi-orientation
title_full Shugoshin-1 Balances Aurora B Kinase Activity via PP2A to Promote Chromosome Bi-orientation
title_fullStr Shugoshin-1 Balances Aurora B Kinase Activity via PP2A to Promote Chromosome Bi-orientation
title_full_unstemmed Shugoshin-1 Balances Aurora B Kinase Activity via PP2A to Promote Chromosome Bi-orientation
title_short Shugoshin-1 Balances Aurora B Kinase Activity via PP2A to Promote Chromosome Bi-orientation
title_sort shugoshin-1 balances aurora b kinase activity via pp2a to promote chromosome bi-orientation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4718550/
https://www.ncbi.nlm.nih.gov/pubmed/25892238
http://dx.doi.org/10.1016/j.celrep.2015.03.052
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