Affinage

BUB1B

Mitotic checkpoint serine/threonine-protein kinase BUB1 beta · UniProt O60566

Length
1050 aa
Mass
119.5 kDa
Annotated
2026-04-28
100 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BUB1B encodes BubR1, a pseudokinase scaffold that serves dual roles in mitotic fidelity: enforcing the spindle assembly checkpoint (SAC) and stabilizing kinetochore–microtubule attachments. BubR1 inhibits APC/C^Cdc20 through direct KEN-box–mediated binding of Cdc20, acting in concert with Bub3 and Mad2 to generate the mitotic checkpoint complex; this inhibitory activity is independent of its kinase domain, which is catalytically degenerate in vertebrates yet essential for protein stability (PMID:11702782, PMID:11907259, PMID:22698286). BubR1 localizes to kinetochores via two routes—heterodimerization with Bub1 (the major pool, required for chromosome alignment) and direct Bub3-dependent binding to phospho-MELT repeats on KNL1 (a minor pool required for SAC signaling)—and recruits PP2A-B56α through a PLK1/CDK1-phosphorylated LxxIxE/KARD motif, counteracting Aurora B to stabilize kinetochore–microtubule attachments (PMID:23079597, PMID:27350047, PMID:27457023). BubR1 protein levels are maintained by SIRT2-mediated deacetylation at K668, and its checkpoint-silencing is coupled to CENP-E–dependent microtubule capture at kinetochores (PMID:24825348, PMID:12859900).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 High

    Establishing that BubR1 is a mitotic checkpoint kinase that localizes to kinetochores and associates with APC/C answered the question of whether a second BUB1-family kinase participates directly in checkpoint signaling in human cells.

    Evidence Co-IP, kinase assays, dominant-negative expression in synchronized human cells

    PMID:10477750

    Open questions at the time
    • Substrate identity of kinase activity unknown
    • Whether kinase activity is required for checkpoint function unclear
    • Mechanism of APC/C interaction undefined
  2. 2001 High

    Demonstrating that purified BubR1–Bub3 directly inhibits APC/C^Cdc20 independently of Mad2 and without requiring kinase activity resolved a key question about how the checkpoint signal converges on APC/C and revealed a kinase-independent inhibitory mechanism.

    Evidence Biochemical purification and in vitro APC/C assays with purified BubR1–Bub3, Xenopus extract reconstitution

    PMID:11702782 PMID:11907259

    Open questions at the time
    • How Mad2 and BubR1 cooperate mechanistically at the structural level
    • Identity of critical BubR1 residues for Cdc20 interaction
  3. 2003 High

    Identification of CENP-E as the activating ligand for BubR1 kinase activity—and silencing of that activity upon microtubule capture—solved the problem of how kinetochore attachment status is transduced into checkpoint signaling.

    Evidence In vitro reconstitution with purified BubR1, CENP-E, and microtubules; Xenopus egg extracts

    PMID:12859900 PMID:16144904

    Open questions at the time
    • In vivo significance of BubR1 kinase activity vs. scaffolding role contested
    • Substrates of BubR1 kinase in checkpoint silencing not fully identified
  4. 2003 High

    Showing that Aurora B activity is required for BubR1 kinetochore localization and its rebinding upon loss of tension established Aurora B as an upstream regulator linking tension sensing to checkpoint protein dynamics.

    Evidence Aurora kinase inhibitor (ZM447439), RNAi, immunofluorescence in human cells

    PMID:12719470

    Open questions at the time
    • Whether Aurora B directly phosphorylates BubR1 or acts indirectly
    • Precise phosphosites responsible for localization unresolved
  5. 2004 High

    Demonstrating that BubR1 depletion causes unstable (not absent) kinetochore–microtubule attachments rescued by Aurora B inhibition revealed that BubR1 functions to counterbalance Aurora B destabilization, beyond its SAC role.

    Evidence RNAi depletion, live imaging, phospho-CENP-A detection in human cells

    PMID:15592459

    Open questions at the time
    • Molecular mechanism by which BubR1 opposes Aurora B not yet identified
  6. 2007 High

    Mapping CDK1-dependent PLK1 recruitment to BubR1 (T620→S676 phosphorylation cascade) and showing tension-dependent dephosphorylation of S676 answered how PLK1 is targeted to BubR1 and how this phosphorylation governs chromosome alignment.

    Evidence In vitro kinase assay, mass spectrometry, phospho-specific antibodies, mutagenesis with functional rescue

    PMID:17376779 PMID:17785528

    Open questions at the time
    • Identity of the phosphatase responsible for S676 dephosphorylation at metaphase
    • How PLK1 phosphorylation of BubR1 mechanistically stabilizes attachments
  7. 2010 High

    Systematic mutagenesis separating KEN-box (SAC), GLEBS motif (kinetochore recruitment via Bub3), and proline-directed phosphosites (chromosome alignment) established BubR1 as a modular scaffold with genetically separable checkpoint and attachment functions.

    Evidence Mass spectrometry-based phosphomapping, systematic mutagenesis with functional readouts in human cells

    PMID:20016069 PMID:20220147

    Open questions at the time
    • How the TPR domain coordinates Blinkin/Bub1 binding at the structural level
  8. 2012 High

    Three concurrent studies resolved longstanding questions: BubR1 is a vertebrate pseudokinase dispensable for catalysis but requiring ATP binding for stability; PLK1 phosphorylation of the KARD motif directly recruits PP2A-B56α to kinetochores to oppose Aurora B; and CENP-E-dependent autophosphorylation contributes to checkpoint strength.

    Evidence Evolutionary analysis with mutagenesis and in vivo complementation; reciprocal Co-IP and phospho-substrate assays; autophosphorylation assays with non-phosphorylatable mutants

    PMID:22698286 PMID:22801780 PMID:23079597

    Open questions at the time
    • Whether residual kinase activity has any physiological role in specific contexts
    • How PP2A-B56α recruitment is regulated during the metaphase-anaphase transition
  9. 2014 High

    Discovery that SIRT2 deacetylates BubR1-K668 to maintain its protein stability, and that age-related NAD+ decline leads to CBP-mediated acetylation and degradation of BubR1, established a post-translational mechanism linking metabolic aging to checkpoint erosion.

    Evidence Acetylation site mutagenesis, SIRT2 overexpression/knockout, NMN supplementation in mice

    PMID:24825348

    Open questions at the time
    • Whether acetylation-dependent degradation uses a specific E3 ligase
    • Relevance to human aging not directly tested
  10. 2015 High

    Reconstitution and chimera experiments demonstrated that BubR1 reaches kinetochores primarily through direct heterodimerization with Bub1 at a pseudo-symmetric interface, while a minor Bub3-dependent pool on KNL1 MELT repeats is specifically required for SAC signaling, uncoupling localization from checkpoint function.

    Evidence Chimeric protein expression, defined mutants, kinetochore recruitment and checkpoint assays

    PMID:25611342 PMID:26031201 PMID:27457023

    Open questions at the time
    • How the minor MELT-bound pool is selectively channeled into MCC assembly
    • Stoichiometry of the two pools at individual kinetochores unknown
  11. 2016 High

    Crystal structure of the PP2A-B56–BubR1 complex at 1.8 Å revealed the LxxIxE motif docking into a groove on B56 HEAT repeats 3–4, providing the atomic basis for how BubR1 recruits PP2A to kinetochores.

    Evidence X-ray crystallography with biochemical validation

    PMID:27350047

    Open questions at the time
    • Structural basis for phosphorylation-dependent regulation of the LxxIxE motif binding
    • Full-length BubR1 structure at kinetochore not resolved
  12. 2020 Medium

    Mapping the BubR1 C-terminal basic helix as necessary for CENP-E interaction defined the molecular interface through which BubR1 recruits CENP-E to kinetochores for chromosome congression.

    Evidence Domain mutagenesis, Co-IP, kinetochore localization assays with RNAi rescue

    PMID:32665320

    Open questions at the time
    • Structural detail of the BubR1–CENP-E interface lacking
    • Whether other proteins bridge or stabilize this interaction in vivo
  13. 2021 Medium

    Finding that elevated BUB1B promotes mutagenic NHEJ and physically interacts with phospho-ATM after irradiation raised the possibility that BubR1 has a non-mitotic role in the DNA damage response.

    Evidence CRISPR-based DNA repair assay, Co-IP of pATM–BUB1B, ATM inhibitor rescue

    PMID:34545188

    Open questions at the time
    • Mechanism by which BubR1 promotes NHEJ is unknown
    • Whether the pATM interaction is direct or mediated by a bridging factor
    • Not independently replicated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full structural basis of BubR1 at the kinetochore (no full-length structure in context of the KMN network), whether residual catalytic activity has any physiological role, how the two kinetochore pools are dynamically regulated during error correction, and the in vivo relevance of non-mitotic functions (ciliogenesis, DNA repair).
  • No full-length BubR1 structure in kinetochore context
  • Physiological significance of pseudokinase catalytic activity unresolved
  • Non-mitotic roles lack independent replication

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0060090 molecular adaptor activity 3 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005694 chromosome 5 GO:0005829 cytosol 2
Pathway
R-HSA-1640170 Cell Cycle 7 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 1
Partners
BUB1BUB3CASC5CDC20CENPEMAD2L1PLK1PPP2R5A
Complex memberships
BubR1–Bub3Mitotic checkpoint complex (MCC)PP2A-B56α–BubR1

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 hBUBR1 is an essential mitotic checkpoint kinase that localizes to kinetochores during mitosis, monitors CENP-E-dependent kinetochore activities, and associates with the cyclosome/APC in mitotically arrested cells but not in interphase cells. Its kinase activity is stimulated upon spindle disruption. Immunoprecipitation, kinase assays, dominant-negative expression, cell synchronization The Journal of cell biology High 10477750
2001 BubR1-Bub3 complex purified from mitotic human cells inhibits APC/C(Cdc20) in a Mad2-independent manner by blocking Cdc20 binding to APC; this inhibition does not require BubR1 kinase activity. BubR1 also interacts with the mitotic motor CENP-E. Biochemical purification, in vitro APC/C activity assay, immunoprecipitation, Xenopus egg extract reconstitution Developmental cell High 11702782
2002 BubR1 directly binds Cdc20 and inhibits APC/C activation independently of its kinase activity; BubR1 is 12-fold more potent than Mad2 as an APC/C inhibitor, and BubR1 and Mad2 synergistically inhibit Cdc20-APC at physiological concentrations by mutually promoting each other's binding to Cdc20. In vitro APC/C ubiquitylation assay, recombinant protein binding, quantitative analysis Molecular biology of the cell High 11907259
2003 CENP-E directly activates BubR1 kinase activity; microtubule capture by the CENP-E motor domain silences BubR1 kinase activity in a ternary BubR1-CENP-E-microtubule complex, establishing CENP-E as the signal transducer that links kinetochore microtubule capture to checkpoint silencing. Purified component reconstitution with CENP-E and BubR1, Xenopus egg extracts, kinase assays Cell High 12859900
2003 Aurora B kinase activity is required for kinetochore localization of BubR1 (and Mad2 and CENP-E), for phosphorylation of BubR1 on mitotic entry, and for rebinding of BubR1 to metaphase kinetochores after reduction in centromeric tension. BubR1 is also required for chromosome alignment, not only spindle checkpoint function. Aurora kinase inhibitor (ZM447439), RNA interference, immunofluorescence, Western blot The Journal of cell biology High 12719470
2004 BubR1 depletion in human cells causes failure to form stable kinetochore-microtubule attachments (not failure to bind microtubules), increases phosphorylation of the Aurora kinase substrate CENP-A at kinetochores, and this defect is rescued by Aurora kinase inhibition. RNAi depletion, live imaging, immunofluorescence, phospho-specific antibody Nature cell biology High 15592459
2005 Microtubule capture by the CENP-E motor domain constitutively silences BubR1 kinase activity in vitro using purified BubR1, CENP-E, and microtubules, confirming a ternary complex-based silencing mechanism. In vitro kinase assay with purified BubR1, CENP-E, and microtubules The Journal of cell biology High 16144904
2007 BubR1 is phosphorylated by Cdk1 on T620, which recruits Plk1 to BubR1; Plk1 then phosphorylates BubR1 on S676. S676 phosphorylation is tension-sensitive: it is present during prometaphase but dephosphorylated at metaphase upon establishment of sister chromatid tension. This phosphorylation is required for stable kinetochore-microtubule interactions and chromosome alignment. In vitro kinase assay, quantitative mass spectrometry, phospho-specific antibody, mutagenesis Genes & development High 17785528
2007 BubR1 colocalizes and physically interacts with Plk1 at kinetochores of unaligned chromosomes; Plk1 phosphorylates BubR1 in vitro at two consensus sites in its kinase domain, and phosphomimetic BubR1 rescues chromosome alignment defects in BubR1-deficient cells, demonstrating Plk1 facilitates chromosome alignment through BubR1. Co-immunoprecipitation, in vitro kinase assay, RNAi, rescue with phosphomimetic mutants The Journal of biological chemistry High 17376779
2007 BubR1 interacts with APC/EB1 microtubule plus-end tracking proteins; BubR1 directly phosphorylates APC in vitro and forms a ternary complex with APC and microtubules, providing a link between BubR1 kinase activity and stable kinetochore-microtubule attachment. Immunodepletion from Xenopus egg extracts, in vitro kinase assay with purified components, Co-immunoprecipitation The Journal of cell biology Medium 17709426
2010 BUBR1 has two functionally distinct domains: KEN boxes are required for spindle assembly checkpoint (SAC) function and Cdc20/APC-C binding, while multiple proline-directed phosphorylation sites are required for chromosome-spindle attachment but not SAC. The GLEBS motif is required for Bub3 interaction, kinetochore localization, and both SAC and chromosome congression functions. In vivo phosphorylation mapping by mass spectrometry, mutagenesis, Co-immunoprecipitation, functional assays Journal of cell science High 20016069
2012 BUBR1 is an evolutionary pseudokinase in vertebrates: its kinase catalytic motifs are degenerate and dispensable for error-free chromosome segregation, but residues that interact with ATP are essential for conformational stability of the protein. Evolutionary analysis, mutagenesis, in vivo complementation assay, structural modeling Developmental cell High 22698286
2012 A conserved kinetochore-attachment regulatory domain (KARD) in BUBR1 is phosphorylated by PLK1, promoting direct interaction of BUBR1 with the PP2A-B56α phosphatase subunit. This recruits PP2A-B56α to kinetochores, counteracting Aurora B activity there and stabilizing kinetochore-microtubule attachments. Mutagenesis, Co-immunoprecipitation, kinetochore fractionation, phospho-substrate assays, RNAi Developmental cell High 23079597
2012 CENP-E-dependent BubR1 autophosphorylation occurs at unattached kinetochores and is required for full-strength mitotic checkpoint and chromosome alignment; a non-phosphorylatable BubR1 mutant causes chromosome misalignment and reduces Aurora B-mediated Ndc80 phosphorylation at kinetochores. Autophosphorylation assay, non-phosphorylatable and phosphomimetic mutants, immunofluorescence, RNAi The Journal of cell biology High 22801780
2013 BubR1 directly binds B56 family PP2A regulatory subunits through a conserved motif phosphorylated by Cdk1 and Plk1; two hydrophobic residues flanking S670 are required for B56 binding; BubR1 targets a pool of B56-PP2A to kinetochores, and mutation of these residues impairs metaphase plate formation. In vitro binding assay, mutagenesis, kinetochore fractionation, phosphorylation assays Journal of cell science High 23345399
2014 SIRT2 deacetylates BubR1 at lysine-668 to maintain BubR1 protein stability; with age, declining NAD+ reduces SIRT2 activity, leading to CBP acetyltransferase-mediated acetylation of K668 and BubR1 degradation. Overexpression of SIRT2 or NMN treatment restores BubR1 levels in vivo. Acetylation site mutagenesis, SIRT2 overexpression/knockout, in vivo mouse studies, biochemical assays The EMBO journal High 24825348
2014 Bub3 promotes mitotic checkpoint signaling through two distinct mechanisms: enhancing BubR1 binding to unattached kinetochores and stimulating BubR1's N-terminal Cdc20-binding domain interaction with a site on Cdc20 exposed by initial Mad2 binding, generating the final BubR1-Bub3-Cdc20 mitotic checkpoint complex that inhibits APC/C. In vitro reconstitution, cell-based assays, mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 25246557
2015 BubR1 kinetochore localization relies on direct heterodimerization with Bub1 at a pseudo-symmetric interface; grafting a short Bub1 motif onto BubR1 promotes Bub1-independent kinetochore recruitment of BubR1 but cannot sustain checkpoint function, uncoupling localization from signaling. Mutagenesis, chimeric protein expression, in vitro binding assays, functional complementation eLife High 25611342
2015 Two distinct pools of BubR1/Bub3 exist at kinetochores: a major pool dependent on Bub1 interaction required for chromosome alignment but not SAC, and a minor pool binding directly to phosphorylated MELT repeats on KNL1 required for efficient incorporation into checkpoint complexes and SAC signaling. Defined BubR1/Bub3 mutants, kinetochore recruitment assays, checkpoint activity assays Nature communications High 27457023
2016 Crystal structure of PP2A B56-BubR1 complex shows that a conserved BubR1 LxxIxE motif binds to a groove in the concave side of B56 HEAT repeats 3 and 4, distant from the C subunit binding site, providing structural basis for B56-directed PP2A recruitment to kinetochores via BubR1. X-ray crystallography at 1.8 Å resolution, biochemical validation Protein & cell High 27350047
2010 The N-terminal TPR domain of BubR1 (crystal structure at 1.8 Å) contains a shallow groove on its concave surface that mediates interaction with kinetochore protein Blinkin; BubR1 also directly interacts with Bub1 via regions C-terminal to their TPR domains, providing a mechanism for Bub1-dependent kinetochore recruitment of BubR1. X-ray crystallography, in vitro binding assays, mutagenesis The Journal of biological chemistry High 20220147
2000 BUBR1 directly interacts with p55CDC/hCdc20 (yeast two-hybrid and GST pulldown), and this interaction is enhanced upon spindle checkpoint activation by nocodazole. BUBR1 phosphorylates p55CDC in vitro, and APC components CDC16 and CDC27 preferentially associate with BUBR1 in mitotically arrested cells. Yeast two-hybrid, GST pulldown, co-immunoprecipitation, in vitro kinase assay Oncogene Medium 11030144
2011 BUBR1 is required for primary cilia formation in vertebrates; in G0 phase, BUBR1 mediates ubiquitin-dependent proteasomal degradation of CDC20 and maintains APC/C-CDH1 activity that regulates dishevelled levels for ciliogenesis. Morpholino knockdown of bubr1 in medaka caused ciliary dysfunction and defects in cerebellar development and left-right asymmetry. Morpholino knockdown (medaka), biochemical assays, conditional knockdown in mammalian cells Human molecular genetics Medium 21389084
2006 BubR1 interacts with PARP-1 (identified by affinity pulldown and mass spectrometry, confirmed by reciprocal Co-IP); BubR1 deficiency compromises retention of intact PARP-1 upon DNA damage, linking the spindle checkpoint to the DNA damage response pathway. Affinity pulldown with mass spectrometry, reciprocal co-immunoprecipitation, BubR1 knockout MEFs Oncogene Medium 16449973
2003 BCSG1 (breast cancer-specific gene 1/gamma-synuclein) directly binds BubR1 (identified by yeast two-hybrid, confirmed by Co-IP and GST pulldown) and promotes BubR1 proteasomal degradation, impairing the mitotic checkpoint. Yeast two-hybrid, Co-immunoprecipitation, GST pulldown, proteasome inhibitor rescue Oncogene Low 14576821
2017 Sirt2-mediated deacetylation of BubR1 at lysine-243 regulates meiotic spindle assembly checkpoint and kinetochore-microtubule attachments in mouse oocytes; acetylation-mimetic BubR1-K243Q recapitulates Sirt2-knockdown meiotic defects, and non-acetylatable BubR1-K243R partially rescues meiotic deficits in aged oocytes. Oocyte microinjection, acetylation site mutagenesis, live imaging, immunofluorescence Aging cell Medium 29067790
2020 The basic C-terminal helix of BubR1 is necessary (but not sufficient) for direct interaction with the acidic kinetochore-targeting domain of CENP-E; BubR1 is required for recruitment of CENP-E to kinetochores for chromosome alignment, defining the molecular basis of the BubR1-CENP-E axis. Mutagenesis, Co-immunoprecipitation, kinetochore localization assays, RNAi rescue Journal of cell science Medium 32665320
2021 Increased BUB1B expression promotes mutagenic non-homologous end joining (NHEJ) DNA repair; phosphorylated ATM physically interacts with BUB1B after ionizing radiation, and resistance to DNA double-strand breaks conferred by elevated BUB1B is ATM-dependent. CRISPR/Cas9-based DNA repair assay, Co-immunoprecipitation, ATM inhibitor rescue Oncogene Medium 34545188
2015 Distinct Bub1 domains separately mediate kinetochore localization of RZZ complex and BubR1; Bub1 (not Zwint) is required for RZZ recruitment; a specific Bub1 region mediates direct BubR1 binding for its kinetochore localization, and removal of the BubR1-recruiting Bub1 region paradoxically increases checkpoint strength. Domain deletion analysis, RNAi, kinetochore localization assays Nature communications Medium 26031201

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. The Journal of cell biology 1049 12719470
1996 Yeast HOG1 MAP kinase cascade is regulated by a multistep phosphorelay mechanism in the SLN1-YPD1-SSK1 "two-component" osmosensor. Cell 721 8808622
2004 BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice. Nature genetics 615 15208629
2004 Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nature genetics 477 15475955
2001 Mad2-Independent inhibition of APCCdc20 by the mitotic checkpoint protein BubR1. Developmental cell 356 11702782
1999 Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC. The Journal of cell biology 314 10477750
2008 Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency. Nature cell biology 313 18516091
2007 Tension-sensitive Plk1 phosphorylation on BubR1 regulates the stability of kinetochore microtubule interactions. Genes & development 268 17785528
2004 The human mitotic checkpoint protein BubR1 regulates chromosome-spindle attachments. Nature cell biology 268 15592459
2002 Checkpoint protein BubR1 acts synergistically with Mad2 to inhibit anaphase-promoting complex. Molecular biology of the cell 265 11907259
1998 Activation of the yeast SSK2 MAP kinase kinase kinase by the SSK1 two-component response regulator. The EMBO journal 248 9482735
2001 Mammalian mad2 and bub1/bubR1 recognize distinct spindle-attachment and kinetochore-tension checkpoints. Proceedings of the National Academy of Sciences of the United States of America 241 11274370
2012 Integration of kinase and phosphatase activities by BUBR1 ensures formation of stable kinetochore-microtubule attachments. Developmental cell 220 23079597
2003 Activating and silencing the mitotic checkpoint through CENP-E-dependent activation/inactivation of BubR1. Cell 203 12859900
2014 SIRT2 induces the checkpoint kinase BubR1 to increase lifespan. The EMBO journal 195 24825348
2001 Kinetochore localisation and phosphorylation of the mitotic checkpoint components Bub1 and BubR1 are differentially regulated by spindle events in human cells. Journal of cell science 185 11792804
2010 BUB1 and BUBR1: multifaceted kinases of the cell cycle. Trends in biochemical sciences 175 20888775
2013 Direct binding between BubR1 and B56-PP2A phosphatase complexes regulate mitotic progression. Journal of cell science 172 23345399
2005 CENP-A is required for accurate chromosome segregation and sustained kinetochore association of BubR1. Molecular and cellular biology 163 15870271
2003 Overexpression of the mitotic checkpoint genes BUB1, BUBR1, and BUB3 in gastric cancer--association with tumour cell proliferation. The Journal of pathology 146 12692836
2005 Bub1 and aurora B cooperate to maintain BubR1-mediated inhibition of APC/CCdc20. Journal of cell science 143 16046481
2006 Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome. American journal of medical genetics. Part A 141 16411201
2015 A molecular basis for the differential roles of Bub1 and BubR1 in the spindle assembly checkpoint. eLife 123 25611342
2005 Microtubule capture by CENP-E silences BubR1-dependent mitotic checkpoint signaling. The Journal of cell biology 122 16144904
2000 Defective hyphal development and avirulence caused by a deletion of the SSK1 response regulator gene in Candida albicans. Infection and immunity 117 10639412
2013 p21 both attenuates and drives senescence and aging in BubR1 progeroid mice. Cell reports 111 23602569
2012 The vertebrate mitotic checkpoint protein BUBR1 is an unusual pseudokinase. Developmental cell 108 22698286
2015 Distinct domains in Bub1 localize RZZ and BubR1 to kinetochores to regulate the checkpoint. Nature communications 95 26031201
2010 BubR1 is a spindle assembly checkpoint protein regulating meiotic cell cycle progression of mouse oocyte. Cell cycle (Georgetown, Tex.) 95 20237433
2007 Overexpression of BUBR1 is associated with chromosomal instability in bladder cancer. Cancer genetics and cytogenetics 95 17350465
2010 Molecular causes for BUBR1 dysfunction in the human cancer predisposition syndrome mosaic variegated aneuploidy. Cancer research 94 20516114
2010 Uncoupling of the spindle-checkpoint and chromosome-congression functions of BubR1. Journal of cell science 92 20016069
2003 Breast cancer-specific gene 1 interacts with the mitotic checkpoint kinase BubR1. Oncogene 88 14576821
2002 Mad2 and BubR1 function in a single checkpoint pathway that responds to a loss of tension. Molecular biology of the cell 88 12388768
2007 Polo-like kinase 1 facilitates chromosome alignment during prometaphase through BubR1. The Journal of biological chemistry 80 17376779
2012 Cancer-Specific requirement for BUB1B/BUBR1 in human brain tumor isolates and genetically transformed cells. Cancer discovery 75 23154965
2010 Homozygous BUB1B mutation and susceptibility to gastrointestinal neoplasia. The New England journal of medicine 75 21190457
2015 Mouse oocytes depend on BubR1 for proper chromosome segregation but not for prophase I arrest. Nature communications 73 25897860
2008 Kinetochore-microtubule interactions "in check" by Bub1, Bub3 and BubR1: The dual task of attaching and signalling. Cell cycle (Georgetown, Tex.) 69 18594200
2016 Crystal structure of a PP2A B56-BubR1 complex and its implications for PP2A substrate recruitment and localization. Protein & cell 67 27350047
2010 The Skp1-like protein SSK1 is required for cross-pollen compatibility in S-RNase-based self-incompatibility. The Plant journal : for cell and molecular biology 67 20070569
2006 BubR1 is involved in regulation of DNA damage responses. Oncogene 67 16449973
2005 Transcriptional control of BubR1 by p53 and suppression of centrosome amplification by BubR1. Molecular and cellular biology 62 15870277
2010 BubR1- and Polo-coated DNA tethers facilitate poleward segregation of acentric chromatids. Cell 61 20141837
2020 BUB1B promotes hepatocellular carcinoma progression via activation of the mTORC1 signaling pathway. Cancer medicine 60 32977361
2012 CENP-E--dependent BubR1 autophosphorylation enhances chromosome alignment and the mitotic checkpoint. The Journal of cell biology 60 22801780
2000 p55CDC/hCDC20 is associated with BUBR1 and may be a downstream target of the spindle checkpoint kinase. Oncogene 55 11030144
1999 The mouse mitotic checkpoint gene bub1b, a novel bub1 family member, is expressed in a cell cycle-dependent manner. Genomics 55 9889005
2011 Insufficiency of BUBR1, a mitotic spindle checkpoint regulator, causes impaired ciliogenesis in vertebrates. Human molecular genetics 52 21389084
2007 BubR1 and APC/EB1 cooperate to maintain metaphase chromosome alignment. The Journal of cell biology 52 17709426
2017 The FOXM1/BUB1B signaling pathway is essential for the tumorigenicity and radioresistance of glioblastoma. Oncology reports 51 29039578
2013 TALEN-mediated single-base-pair editing identification of an intergenic mutation upstream of BUB1B as causative of PCS (MVA) syndrome. Proceedings of the National Academy of Sciences of the United States of America 49 24344301
1999 Differential stabilities of phosphorylated response regulator domains reflect functional roles of the yeast osmoregulatory SLN1 and SSK1 proteins. Journal of bacteriology 49 9882653
2021 BUB1B and circBUB1B_544aa aggravate multiple myeloma malignancy through evoking chromosomal instability. Signal transduction and targeted therapy 48 34620840
2009 Separating the spindle, checkpoint, and timer functions of BubR1. The Journal of cell biology 48 19951912
2015 BubR1 kinase: protection against aneuploidy and premature aging. Trends in molecular medicine 47 25964054
2014 Mad2 and BubR1 modulates tumourigenesis and paclitaxel response in MKN45 gastric cancer cells. Cell cycle (Georgetown, Tex.) 46 25483095
2012 Reduced life- and healthspan in mice carrying a mono-allelic BubR1 MVA mutation. PLoS genetics 46 23300461
2007 Transcription of the human cell cycle regulated BUB1B gene requires hStaf/ZNF143. Nucleic acids research 46 17478512
2007 Weakened spindle checkpoint with reduced BubR1 expression in paclitaxel-resistant ovarian carcinoma cell line SKOV3-TR30. Gynecologic oncology 45 17234259
2015 Requirement for BUB1B/BUBR1 in tumor progression of lung adenocarcinoma. Genes & cancer 44 26000094
2012 Identification of FoxM1/Bub1b signaling pathway as a required component for growth and survival of rhabdomyosarcoma. Cancer research 43 23002205
2006 Mutant mice with small amounts of BubR1 display accelerated age-related gliosis. Neurobiology of aging 43 16781018
2008 Overexpression of the mitotic checkpoint genes BUB1 and BUBR1 is associated with genomic complexity in clear cell kidney carcinomas. Cellular oncology : the official journal of the International Society for Cellular Oncology 42 18791270
2023 In Silico Insight to Identify Potential Inhibitors of BUB1B from Mushroom Bioactive Compounds to Prevent Breast Cancer Metastasis. Frontiers in bioscience (Landmark edition) 39 37525917
2017 Sirt2-BubR1 acetylation pathway mediates the effects of advanced maternal age on oocyte quality. Aging cell 39 29067790
2009 The clinicopathological significance of BUBR1 overexpression in hepatocellular carcinoma. Journal of clinical pathology 38 19861558
2007 Spindle proteins Aurora A and BUB1B, but not Mad2, are aberrantly expressed in dysplastic mucosa of patients with longstanding ulcerative colitis. Journal of clinical pathology 38 17322345
2010 Defining the molecular basis of BubR1 kinetochore interactions and APC/C-CDC20 inhibition. The Journal of biological chemistry 37 20220147
2008 Reduced level of the spindle checkpoint protein BUB1B is associated with aneuploidy in colorectal cancers. Cell proliferation 36 18699967
2005 The mitotic checkpoint gene BubR1 has two distinct functions in mitosis. Experimental cell research 35 15907836
2017 Age-related decline in BubR1 impairs adult hippocampal neurogenesis. Aging cell 34 28383136
2013 New insights into the role of BubR1 in mitosis and beyond. International review of cell and molecular biology 34 24016527
2021 Increased BUB1B/BUBR1 expression contributes to aberrant DNA repair activity leading to resistance to DNA-damaging agents. Oncogene 33 34545188
2014 Bimodal activation of BubR1 by Bub3 sustains mitotic checkpoint signaling. Proceedings of the National Academy of Sciences of the United States of America 33 25246557
2016 Prevalence of germline mutations in the spindle assembly checkpoint gene BUB1B in individuals with early-onset colorectal cancer. Genes, chromosomes & cancer 32 27239782
2005 Deletion of the SSK1 response regulator gene in Candida albicans contributes to enhanced killing by human polymorphonuclear neutrophils. Infection and immunity 32 15664927
2020 Spindle assembly checkpoint gene BUB1B is essential in breast cancer cell survival. Breast cancer research and treatment 31 33130993
2017 Sensitivity to BUB1B Inhibition Defines an Alternative Classification of Glioblastoma. Cancer research 31 28855212
2007 Drosophila BubR1 is essential for meiotic sister-chromatid cohesion and maintenance of synaptonemal complex. Current biology : CB 31 17702574
2020 The C-terminal helix of BubR1 is essential for CENP-E-dependent chromosome alignment. Journal of cell science 30 32665320
2016 Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation. Nature communications 30 27457023
2005 Comparative genomic hybridization and BUB1B mutation analyses in childhood cancers associated with mosaic variegated aneuploidy syndrome. Cancer letters 29 16182441
2007 BubR1 and CENP-E have antagonistic effects upon the stability of microtubule-kinetochore attachments in Drosophila S2 cell mitosis. Cell cycle (Georgetown, Tex.) 27 17525528
2007 APC inactivation associates with abnormal mitosis completion and concomitant BUB1B/MAD2L1 up-regulation. Gastroenterology 27 17570218
2016 How the Pathogenic Fungus Alternaria alternata Copes with Stress via the Response Regulators SSK1 and SHO1. PloS one 26 26863027
2022 The spindle checkpoint proteins BUB1 and BUBR1: (SLiM)ming down to the basics. Trends in biochemical sciences 25 35184951
2009 Effects of osmolytes on the SLN1-YPD1-SSK1 phosphorelay system from Saccharomyces cerevisiae. Biochemistry 25 19618914
2016 Association between polymorphisms in segregation genes BUB1B and TTK and gastric cancer risk. Radiology and oncology 24 27679546
2015 Bub3-BubR1-dependent sequestration of Cdc20Fizzy at DNA breaks facilitates the correct segregation of broken chromosomes. The Journal of cell biology 24 26553926
2008 Chromosome damage in mitosis induces BubR1 activation and prometaphase arrest. FEBS letters 23 18440313
2016 The progeroid gene BubR1 regulates axon myelination and motor function. Aging 22 27922816
2010 Recruitment of Cdc20 to the kinetochore requires BubR1 but not Mad2 in Drosophila melanogaster. Molecular and cellular biology 22 20421417
2009 Expression of mitotic checkpoint proteins BUB1B and MAD2L1 in salivary duct carcinomas. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 22 20040022
2009 Ajuba: a new microtubule-associated protein that interacts with BUBR1 and Aurora B at kinetochores in metaphase. Biology of the cell 21 18710370
2008 Gradual reduction of BUBR1 protein levels results in premature sister-chromatid separation then in aneuploidy. Human genetics 21 18932004
2011 Reduced proliferation of aged human vascular smooth muscle cells--role of oxygen-derived free radicals and BubR1 expression. The Journal of surgical research 20 21550059
2019 Nearly complete deletion of BubR1 causes microcephaly through shortened mitosis and massive cell death. Human molecular genetics 19 30668728
2017 The E2F activators control multiple mitotic regulators and maintain genomic integrity through Sgo1 and BubR1. Oncotarget 19 29100415
2015 BUB1B promotes multiple myeloma cell proliferation through CDC20/CCNB axis. Medical oncology (Northwood, London, England) 19 25698537