Cargando…
Spatial separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis
The Bub1 and BubR1 kinetochore proteins support proper chromosome segregation and mitotic checkpoint activity. Bub1 and BubR1 are paralogs with Bub1 being a kinase, while BubR1 localizes the PP2A-B56 protein phosphatase to kinetochores in humans. Whether this spatial separation of kinase and phospha...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10155811/ https://www.ncbi.nlm.nih.gov/pubmed/36441015 http://dx.doi.org/10.1093/jmcb/mjac062 |
_version_ | 1785036407006298112 |
---|---|
author | Wang, Lei Kruse, Thomas López-Méndez, Blanca Zhang, Yuqing Song, Chunlin Zhu, Lei Li, Bing Fang, Jing Lu, Zhimin Nilsson, Jakob Zhang, Gang |
author_facet | Wang, Lei Kruse, Thomas López-Méndez, Blanca Zhang, Yuqing Song, Chunlin Zhu, Lei Li, Bing Fang, Jing Lu, Zhimin Nilsson, Jakob Zhang, Gang |
author_sort | Wang, Lei |
collection | PubMed |
description | The Bub1 and BubR1 kinetochore proteins support proper chromosome segregation and mitotic checkpoint activity. Bub1 and BubR1 are paralogs with Bub1 being a kinase, while BubR1 localizes the PP2A-B56 protein phosphatase to kinetochores in humans. Whether this spatial separation of kinase and phosphatase activity is important is unclear as some organisms integrate both activities into one Bub protein. Here, we engineer human Bub1 and BubR1 proteins integrating kinase and phosphatase activities into one protein and show that these do not support normal mitotic progression. A Bub1–PP2A-B56 complex can support chromosome alignment but results in impairment of the checkpoint due to dephosphorylation of the Mad1 binding site in Bub1. Furthermore, a chimeric BubR1 protein containing the Bub1 kinase domain induces delocalized H2ApT120 phosphorylation, resulting in the reduction of centromeric hSgo2 and chromosome segregation errors. Collectively, these results argue that the spatial separation of kinase and phosphatase activities within the Bub complex is required for balancing its functions in the checkpoint and chromosome alignment. |
format | Online Article Text |
id | pubmed-10155811 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-101558112023-05-04 Spatial separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis Wang, Lei Kruse, Thomas López-Méndez, Blanca Zhang, Yuqing Song, Chunlin Zhu, Lei Li, Bing Fang, Jing Lu, Zhimin Nilsson, Jakob Zhang, Gang J Mol Cell Biol Article The Bub1 and BubR1 kinetochore proteins support proper chromosome segregation and mitotic checkpoint activity. Bub1 and BubR1 are paralogs with Bub1 being a kinase, while BubR1 localizes the PP2A-B56 protein phosphatase to kinetochores in humans. Whether this spatial separation of kinase and phosphatase activity is important is unclear as some organisms integrate both activities into one Bub protein. Here, we engineer human Bub1 and BubR1 proteins integrating kinase and phosphatase activities into one protein and show that these do not support normal mitotic progression. A Bub1–PP2A-B56 complex can support chromosome alignment but results in impairment of the checkpoint due to dephosphorylation of the Mad1 binding site in Bub1. Furthermore, a chimeric BubR1 protein containing the Bub1 kinase domain induces delocalized H2ApT120 phosphorylation, resulting in the reduction of centromeric hSgo2 and chromosome segregation errors. Collectively, these results argue that the spatial separation of kinase and phosphatase activities within the Bub complex is required for balancing its functions in the checkpoint and chromosome alignment. Oxford University Press 2022-11-28 /pmc/articles/PMC10155811/ /pubmed/36441015 http://dx.doi.org/10.1093/jmcb/mjac062 Text en © The Author(s) (2022). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Article Wang, Lei Kruse, Thomas López-Méndez, Blanca Zhang, Yuqing Song, Chunlin Zhu, Lei Li, Bing Fang, Jing Lu, Zhimin Nilsson, Jakob Zhang, Gang Spatial separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis |
title | Spatial separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis |
title_full | Spatial separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis |
title_fullStr | Spatial separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis |
title_full_unstemmed | Spatial separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis |
title_short | Spatial separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis |
title_sort | spatial separation of phosphatase and kinase activity within the bub complex is required for proper mitosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10155811/ https://www.ncbi.nlm.nih.gov/pubmed/36441015 http://dx.doi.org/10.1093/jmcb/mjac062 |
work_keys_str_mv | AT wanglei spatialseparationofphosphataseandkinaseactivitywithinthebubcomplexisrequiredforpropermitosis AT krusethomas spatialseparationofphosphataseandkinaseactivitywithinthebubcomplexisrequiredforpropermitosis AT lopezmendezblanca spatialseparationofphosphataseandkinaseactivitywithinthebubcomplexisrequiredforpropermitosis AT zhangyuqing spatialseparationofphosphataseandkinaseactivitywithinthebubcomplexisrequiredforpropermitosis AT songchunlin spatialseparationofphosphataseandkinaseactivitywithinthebubcomplexisrequiredforpropermitosis AT zhulei spatialseparationofphosphataseandkinaseactivitywithinthebubcomplexisrequiredforpropermitosis AT libing spatialseparationofphosphataseandkinaseactivitywithinthebubcomplexisrequiredforpropermitosis AT fangjing spatialseparationofphosphataseandkinaseactivitywithinthebubcomplexisrequiredforpropermitosis AT luzhimin spatialseparationofphosphataseandkinaseactivitywithinthebubcomplexisrequiredforpropermitosis AT nilssonjakob spatialseparationofphosphataseandkinaseactivitywithinthebubcomplexisrequiredforpropermitosis AT zhanggang spatialseparationofphosphataseandkinaseactivitywithinthebubcomplexisrequiredforpropermitosis |