Spatial separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis

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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.

In: Journal of Molecular Cell Biology, Vol. 14, No. 11, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Wang, L, Kruse, T, López-Méndez, B, Zhang, Y, Song, C, Zhu, L, Li, B, Fang, J, Lu, Z, Nilsson, J & Zhang, G 2023, 'Spatial separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis', Journal of Molecular Cell Biology, vol. 14, no. 11. https://doi.org/10.1093/jmcb/mjac062

APA

Wang, L., Kruse, T., López-Méndez, B., Zhang, Y., Song, C., Zhu, L., Li, B., Fang, J., Lu, Z., Nilsson, J., & Zhang, G. (2023). Spatial separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis. Journal of Molecular Cell Biology, 14(11). https://doi.org/10.1093/jmcb/mjac062

Vancouver

Wang L, Kruse T, López-Méndez B, Zhang Y, Song C, Zhu L et al. Spatial separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis. Journal of Molecular Cell Biology. 2023;14(11). https://doi.org/10.1093/jmcb/mjac062

Author

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. In: Journal of Molecular Cell Biology. 2023 ; Vol. 14, No. 11.

Bibtex

@article{2ea3f227cd8b4f49859a7578f90d6bee,
title = "Spatial separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis",
abstract = "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.",
keywords = "Humans, Phosphorylation, Cell Cycle Proteins/genetics, Phosphoric Monoester Hydrolases/genetics, Mitosis, Kinetochores/metabolism",
author = "Lei Wang and Thomas Kruse and Blanca L{\'o}pez-M{\'e}ndez and Yuqing Zhang and Chunlin Song and Lei Zhu and Bing Li and Jing Fang and Zhimin Lu and Jakob Nilsson and Gang Zhang",
note = "{\textcopyright} The Author(s) (2022). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.",
year = "2023",
doi = "10.1093/jmcb/mjac062",
language = "English",
volume = "14",
journal = "Journal of Molecular Cell Biology",
issn = "1674-2788",
publisher = "Oxford University Press",
number = "11",

}

RIS

TY - JOUR

T1 - Spatial separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis

AU - Wang, Lei

AU - Kruse, Thomas

AU - López-Méndez, Blanca

AU - Zhang, Yuqing

AU - Song, Chunlin

AU - Zhu, Lei

AU - Li, Bing

AU - Fang, Jing

AU - Lu, Zhimin

AU - Nilsson, Jakob

AU - Zhang, Gang

N1 - © The Author(s) (2022). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Humans

KW - Phosphorylation

KW - Cell Cycle Proteins/genetics

KW - Phosphoric Monoester Hydrolases/genetics

KW - Mitosis

KW - Kinetochores/metabolism

U2 - 10.1093/jmcb/mjac062

DO - 10.1093/jmcb/mjac062

M3 - Journal article

C2 - 36441015

VL - 14

JO - Journal of Molecular Cell Biology

JF - Journal of Molecular Cell Biology

SN - 1674-2788

IS - 11

ER -

ID: 346587397