Self-priming of Plk1 binding to BubR1 ensures accurate mitotic progression
Abstract Plk1 is a key mitotic kinase that localizes to distinct subcellular structures to promote accurate mitotic progression. Plk1 recruitment depends on direct interaction between polo-box domain (PBD) on Plk1 and PBD binding motif (PBD BM) on the interactors. However, recent study showed that P...
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Nature Portfolio
2024-11-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07205-2 |
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| author | Chunlin Song Mingzhe Zhang Thomas Kruse Mads Harder Møller Blanca López-Méndez Yuqing Zhang Yujing Zhai Ying Wang Tingting Lei Arminja N. Kettenbach Jakob Nilsson Gang Zhang |
| author_facet | Chunlin Song Mingzhe Zhang Thomas Kruse Mads Harder Møller Blanca López-Méndez Yuqing Zhang Yujing Zhai Ying Wang Tingting Lei Arminja N. Kettenbach Jakob Nilsson Gang Zhang |
| author_sort | Chunlin Song |
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| description | Abstract Plk1 is a key mitotic kinase that localizes to distinct subcellular structures to promote accurate mitotic progression. Plk1 recruitment depends on direct interaction between polo-box domain (PBD) on Plk1 and PBD binding motif (PBD BM) on the interactors. However, recent study showed that PBD BM alone is not enough for stable binding between CENP-U and Plk1 highlighting the complexity of the interaction which warrants further investigation. An important interactor for Plk1 during mitosis is the checkpoint protein BubR1. Plk1 bound to BubR1 via PBD interaction with pT620 phosphorylates BubR1 S676/T680 to promote BubR1-PP2A/B56 interaction. The BubR1-PP2A/B56 complex counteracts the destablizing effect on kinetochore-microtubule attachments by mitotic kinases to promote mitotic progression. Here we show that Plk1 phosphorylates T600/T608 on BubR1 and the double phosphorylation is critical for BubR1-Plk1 interaction. A similar mechanism for Plk1-Bub1 interaction also exists indicating a general principle for Plk1 kinetochore recruitment through self-priming. Mechanistically preventing BubR1 T600/T608 phosphorylation impairs chromosome congression and checkpoint silencing by reducing Plk1 and PP2A/B56 binding to BubR1. Increasing the binding affinity towards Plk1 and PP2A/B56 in BubR1 through protein engineering bypasses the requirement of T600/T608 phosphorylation for mitotic progression. These results reveal a new layer of regulation for accurate mitotic progression. |
| format | Article |
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| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
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| series | Communications Biology |
| spelling | doaj-art-ece991e00281497d80b9a72cab0b61582025-08-20T02:13:55ZengNature PortfolioCommunications Biology2399-36422024-11-017111110.1038/s42003-024-07205-2Self-priming of Plk1 binding to BubR1 ensures accurate mitotic progressionChunlin Song0Mingzhe Zhang1Thomas Kruse2Mads Harder Møller3Blanca López-Méndez4Yuqing Zhang5Yujing Zhai6Ying Wang7Tingting Lei8Arminja N. Kettenbach9Jakob Nilsson10Gang Zhang11The Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao UniversityThe Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao UniversityNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenThe Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao UniversitySchool of Public Health, Qingdao UniversitySchool of Public Health, Qingdao UniversityThe Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao UniversityDepartment of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth CollegeNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenThe Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao UniversityAbstract Plk1 is a key mitotic kinase that localizes to distinct subcellular structures to promote accurate mitotic progression. Plk1 recruitment depends on direct interaction between polo-box domain (PBD) on Plk1 and PBD binding motif (PBD BM) on the interactors. However, recent study showed that PBD BM alone is not enough for stable binding between CENP-U and Plk1 highlighting the complexity of the interaction which warrants further investigation. An important interactor for Plk1 during mitosis is the checkpoint protein BubR1. Plk1 bound to BubR1 via PBD interaction with pT620 phosphorylates BubR1 S676/T680 to promote BubR1-PP2A/B56 interaction. The BubR1-PP2A/B56 complex counteracts the destablizing effect on kinetochore-microtubule attachments by mitotic kinases to promote mitotic progression. Here we show that Plk1 phosphorylates T600/T608 on BubR1 and the double phosphorylation is critical for BubR1-Plk1 interaction. A similar mechanism for Plk1-Bub1 interaction also exists indicating a general principle for Plk1 kinetochore recruitment through self-priming. Mechanistically preventing BubR1 T600/T608 phosphorylation impairs chromosome congression and checkpoint silencing by reducing Plk1 and PP2A/B56 binding to BubR1. Increasing the binding affinity towards Plk1 and PP2A/B56 in BubR1 through protein engineering bypasses the requirement of T600/T608 phosphorylation for mitotic progression. These results reveal a new layer of regulation for accurate mitotic progression.https://doi.org/10.1038/s42003-024-07205-2 |
| spellingShingle | Chunlin Song Mingzhe Zhang Thomas Kruse Mads Harder Møller Blanca López-Méndez Yuqing Zhang Yujing Zhai Ying Wang Tingting Lei Arminja N. Kettenbach Jakob Nilsson Gang Zhang Self-priming of Plk1 binding to BubR1 ensures accurate mitotic progression Communications Biology |
| title | Self-priming of Plk1 binding to BubR1 ensures accurate mitotic progression |
| title_full | Self-priming of Plk1 binding to BubR1 ensures accurate mitotic progression |
| title_fullStr | Self-priming of Plk1 binding to BubR1 ensures accurate mitotic progression |
| title_full_unstemmed | Self-priming of Plk1 binding to BubR1 ensures accurate mitotic progression |
| title_short | Self-priming of Plk1 binding to BubR1 ensures accurate mitotic progression |
| title_sort | self priming of plk1 binding to bubr1 ensures accurate mitotic progression |
| url | https://doi.org/10.1038/s42003-024-07205-2 |
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