ArticleCell research2019
BubR1 phosphorylates CENP-E as a switch enabling the transition from lateral association to end-on capture of spindle microtubules.
Article in Cell research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 44 citations in OpenAlex.
- Probing Centromere Plasticity and Chromatin Remodeling Using Single-Molecule Techniques.Cell biology international · 2026Review
- Condensation of MATCAP promotes CENP-E-dependent chromosome congression in mitosis.Nature communications · 2026Article
- CENP-E initiates chromosome congression by opposing Aurora kinases to promote end-on attachments.Nature communications · 2025Article
- Kinetochore-centrosome feedback linking CENP-E and Aurora kinases controls chromosome congression.Nature communications · 2025Article
- Akt-elicited phosphorylation of Acapin steers cell migration.Journal of molecular cell biology · 2025Article
- Probing centromere-kinetochore core complex CENP-L/M assembly using cenpemlin.Journal of molecular cell biology · 2025Article
- BubR1 and SIRT2: Insights into aneuploidy, aging, and cancer.Seminars in cancer biology · 2024Review
- Chromothripsis: an emerging crossroad from aberrant mitosis to therapeutic opportunities.Journal of molecular cell biology · 2024Review
- The Role of Molecular and Cellular Aging Pathways on Age-Related Hearing Loss.International journal of molecular sciences · 2024Review
- Meiosis-specific functions of kinetochore protein SPC105R required for chromosome segregation inMolecular biology of the cell · 2024Article
- Organization of microtubule plus-end dynamics by phase separation in mitosis.Journal of molecular cell biology · 2024Article
- PLK1 phosphorylation of ZW10 guides accurate chromosome segregation in mitosis.Journal of molecular cell biology · 2024Article
- Kinetoplastid kinetochore proteins KKT14-KKT15 are divergent Bub1/BubR1-Bub3 proteins.Open biology · 2024Article
- LncRNA TubAR complexes with TUBB4A and TUBA1A to promote microtubule assembly and maintain myelination.Cell discovery · 2024Article
- Kinesin-7 CENP-E mediates chromosome alignment and spindle assembly checkpoint in meiosis I.Chromosoma · 2024Article
- CKAP5 stabilizes CENP-E at kinetochores by regulating microtubule-chromosome attachments.EMBO reports · 2024Article
- Meiosis-specific functions of kinetochore protein SPC105R required for chromosome segregation inbioRxiv : the preprint server for biology · 2024Article
- Phosphorylation of Bub1 by Mph1 promotes Bub1 signaling at the kinetochore to ensure accurate chromosome segregation.The Journal of biological chemistry · 2024Article
- Dynamic phosphorylation of CENP-N by CDK1 guides accurate chromosome segregation in mitosis.Journal of molecular cell biology · 2023Article
- Spatial separation of phosphatase and kinase activity within the Bub complex is required for proper mitosis.Journal of molecular cell biology · 2023Article
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23 authors at 3 institutions in 2 countries.
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Abstract
Error-free mitosis depends on accurate chromosome attachment to spindle microtubules, powered congression of those chromosomes, their segregation in anaphase, and assembly of a spindle midzone at mitotic exit. The centromere-associated kinesin motor CENP-E, whose binding partner is BubR1, has been implicated in congression of misaligned chromosomes and the transition from lateral kinetochore-microtubule association to end-on capture. Although previously proposed to be a pseudokinase, here we report the structure of the kinase domain of Drosophila melanogaster BubR1, revealing its folding into a conformation predicted to be catalytically active. BubR1 is shown to be a bona fide kinase whose phosphorylation of CENP-E switches it from a laterally attached microtubule motor to a plus-end microtubule tip tracker. Computational modeling is used to identify bubristatin as a selective BubR1 kinase antagonist that targets the αN1 helix of N-terminal extension and αC helix of the BubR1 kinase domain. Inhibition of CENP-E phosphorylation is shown to prevent proper microtubule capture at kinetochores and, surprisingly, proper assembly of the central spindle at mitotic exit. Thus, BubR1-mediated CENP-E phosphorylation produces a temporal switch that enables transition from lateral to end-on microtubule capture and organization of microtubules into stable midzone arrays.
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