Affinage

BUB1B

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

Length
1050 aa
Mass
119.5 kDa
Annotated
2026-06-09
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BUB1B (BubR1) is a dual-function mitotic regulator that both enforces the spindle assembly checkpoint (SAC) and promotes chromosome alignment, with these two activities residing in genetically separable modules (PMID:20016069, PMID:19951912, PMID:15907836). As a core component of the Mitotic Checkpoint Complex, BubR1 inhibits APC/C-Cdc20: its N-terminal KEN box binds Cdc20 and it directly engages closed MAD2 through MAD2 residues Arg133/Gln134, while the BubR1:Bub3 module requires phosphorylation-dependent recognition of its targets to inhibit APC/C (PMID:20016069, PMID:21525009, PMID:28943088). Kinetochore recruitment of BubR1/Bub3 occurs through two pools — a Bub1/Bub3-dependent pool driving alignment and a separate pool binding phosphorylated MELT repeats on KNL1 that supports robust checkpoint signaling (PMID:27457023). Beyond checkpoint control, BubR1 stabilizes kinetochore-microtubule attachments by recruiting PP2A-B56 phosphatase: PLK1/CDK1 phosphorylation of the conserved KARD/LxxIxE motif (around Ser670) creates a docking site that binds the concave groove of B56 pseudo-HEAT repeats, delivering PP2A to counteract Aurora B activity at improperly attached kinetochores (PMID:23079597, PMID:23345399, PMID:27350047). BubR1 also recruits CENP-E to kinetochores via its C-terminal basic helix to rescue chromosomes that fail other congression pathways, and CENP-E reciprocally controls BubR1 catalytic state — activating it at unattached kinetochores and silencing it upon microtubule capture in a ternary BubR1-CENP-E-microtubule complex (PMID:12859900, PMID:16144904, PMID:32665320). Although vertebrate BubR1 has degenerated into a pseudokinase whose catalysis is dispensable for error-free segregation, its ATP-binding residues remain essential for conformational stability (PMID:22698286). BubR1 abundance and activity are set by transcriptional inputs from p53 and hStaf/ZNF143 and by post-translational control, including SIRT2-dependent deacetylation that maintains protein stability and segregation fidelity (PMID:24825348, PMID:17478512, PMID:15870277). BubR1 haploinsufficiency causes premature sister-chromatid separation and, at deeper loss, aneuploidy (PMID:18932004).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2003 High

    Established how BubR1 catalytic state is coupled to the physical state of the kinetochore, answering how attachment status is transduced into a checkpoint signal.

    Evidence In vitro reconstitution with purified BubR1, CENP-E, and microtubules plus Xenopus egg extract depletion/add-back

    PMID:12859900

    Open questions at the time
    • Did not resolve which BubR1 substrates are phosphorylated upon activation
    • Vertebrate pseudokinase status later complicated the kinase interpretation
  2. 2003 High

    Placed BubR1 downstream of Aurora B for kinetochore localization and showed BubR1 has an alignment role beyond the checkpoint.

    Evidence Aurora B inhibitor ZM447439, RNAi, and live-cell imaging in human cells

    PMID:12719470

    Open questions at the time
    • Mechanism linking Aurora B activity to BubR1 retention under tension not defined
    • Did not separate checkpoint from attachment contributions molecularly
  3. 2004 High

    Demonstrated BubR1 stabilizes kinetochore-microtubule attachments by limiting Aurora B substrate phosphorylation, foreshadowing a phosphatase-counterbalancing role.

    Evidence siRNA depletion with Aurora inhibition rescue and CENP-A phosphorylation readout in human cells

    PMID:15592459

    Open questions at the time
    • Did not identify the phosphatase BubR1 recruits
    • Direct vs indirect effect on Aurora B unresolved at this stage
  4. 2005 Medium

    Resolved BubR1 into separable N-terminal checkpoint (GLEBS/Bub3) and C-terminal kinase-domain alignment modules.

    Evidence Domain deletion and kinase-dead mutants with mitotic timing in HeLa cells

    PMID:15907836

    Open questions at the time
    • Single lab
    • Kinase-dependence of alignment later reframed by pseudokinase findings
  5. 2005 Medium

    Identified p53 as a transcriptional regulator of BubR1, linking BubR1 dosage to genome stability.

    Evidence Microarray/RT-PCR and re-expression rescue in p53-null mouse cells

    PMID:15870277

    Open questions at the time
    • Direct vs indirect transcriptional control not fully established
    • Single lab
  6. 2005 Medium

    Showed BubR1-containing MCC binding to APC/C requires convergent Bub1 and Aurora B kinase signals.

    Evidence Bub1 RNAi plus Aurora inhibitor with MCC-APC/C co-IP in human cells

    PMID:16046481

    Open questions at the time
    • Redundancy mechanism between the two kinase arms not defined
    • Single lab
  7. 2006 Medium

    Linked BubR1 to the DNA damage response through a physical interaction with PARP-1.

    Evidence Affinity-MS and reciprocal co-IP with damage assays in BubR1+/- MEFs

    PMID:16449973

    Open questions at the time
    • Functional significance of PARP-1 binding for repair not mechanistically resolved
    • Single lab
  8. 2007 High

    Placed PLK1 phosphorylation of BubR1 in the chromosome alignment pathway.

    Evidence In vitro Plk1 kinase assay, phospho-mutant rescue, and epistasis in BubR1-deficient cells

    PMID:17376779

    Open questions at the time
    • Downstream effector of these phospho-sites not identified at this stage
    • Relationship to later KARD/PP2A motif not yet drawn
  9. 2007 Medium

    Identified hStaf/ZNF143 and cell-cycle promoter elements driving G2/M-specific BUB1B transcription.

    Evidence Gel shift, promoter-reporter mutagenesis, and ChIP

    PMID:17478512

    Open questions at the time
    • Single lab
    • Interplay with p53 control not addressed
  10. 2010 High

    Provided a systematic separation-of-function map distinguishing SAC (KEN/GLEBS) from attachment (proline-directed phospho-sites).

    Evidence MS phospho-site mapping, mutagenesis, co-IP, and live imaging in human cells

    PMID:20016069

    Open questions at the time
    • Effectors of the proline-directed sites not all identified
    • How GLEBS/Bub3 binding triggers kinetochore loading not structurally resolved
  11. 2011 High

    Defined the molecular basis of BubR1 engagement with closed MAD2 essential for MCC-mediated APC/C inhibition.

    Evidence Co-IP, MAD2 mutagenesis, and in vitro APC/C inhibition assays

    PMID:21525009

    Open questions at the time
    • How MAD2 alpha-C helix coordinates activation vs silencing not fully resolved
  12. 2012 High

    Resolved the phosphatase BubR1 recruits, defining the PLK1-phosphorylated KARD-PP2A-B56 axis that counters Aurora B at kinetochores.

    Evidence Domain/phospho-mutagenesis, reciprocal co-IP, Aurora B substrate and rescue assays (independently replicated)

    PMID:23079597 PMID:23345399

    Open questions at the time
    • Spatial regulation of PP2A delivery during attachment maturation not fully timed
  13. 2012 High

    Reframed vertebrate BubR1 as a pseudokinase whose catalysis is dispensable but whose ATP-binding residues stabilize conformation.

    Evidence Comparative genomics with kinase-dead complementation in human cells

    PMID:22698286

    Open questions at the time
    • Reconciliation with earlier kinase-activity reports across species incomplete
  14. 2012 High

    Showed CENP-E-dependent BubR1 autophosphorylation supports full checkpoint strength and alignment in human cells.

    Evidence In vitro kinase assay, phospho-mutants, CENP-E depletion, and live imaging

    PMID:22801780

    Open questions at the time
    • Difficult to reconcile with pseudokinase model in same year
    • Relevant in vivo substrates not pinned down
  15. 2014 High

    Established NAD+/SIRT2 deacetylation at K668 as a determinant of BubR1 stability with organismal lifespan consequences.

    Evidence Acetylation-site mutagenesis, CBP identification, NMN and SIRT2-overexpression in mice with lifespan analysis

    PMID:24825348

    Open questions at the time
    • How K668 acetylation triggers turnover mechanistically not fully defined
  16. 2016 High

    Provided a crystal structure showing the BubR1 LxxIxE motif binds the B56 concave groove without occluding catalytic or shugoshin surfaces.

    Evidence X-ray crystallography with biochemical binding assays

    PMID:27350047

    Open questions at the time
    • Single lab
    • Dynamics of phospho-dependent binding in cells not captured
  17. 2016 High

    Distinguished two kinetochore BubR1/Bub3 pools with separable alignment vs checkpoint roles.

    Evidence Binding-mutant dissection, kinetochore localization, SAC assays, and co-IP

    PMID:27457023

    Open questions at the time
    • Quantitative partitioning between pools during mitosis not measured
  18. 2017 High

    Identified a BubR1-specific loop required for APC/C inhibition, showing BubR1:Bub3 needs phosphorylation to target APC/C distinctly from Bub1.

    Evidence In vitro APC/C inhibition and MCC assembly with mutagenesis and cellular SAC assays

    PMID:28943088

    Open questions at the time
    • Identity of the phosphorylated APC/C target recognized by BubR1:Bub3 not defined
  19. 2020 High

    Mapped the reciprocal BubR1 C-terminal basic helix / CENP-E acidic patch interaction required for CENP-E kinetochore recruitment and rescue congression.

    Evidence Domain mutagenesis, co-IP, localization, and alignment rescue in human cells

    PMID:32665320

    Open questions at the time
    • Single lab
    • How this axis is regulated relative to PP2A recruitment not addressed
  20. 2021 Medium

    Connected aberrant BUB1B expression to mutagenic NHEJ via an ATM interaction, with FOXM1 driving BUB1B upregulation in recurrent cancer.

    Evidence Phospho-ATM co-IP, CRISPR repair-pathway analysis, ATM inhibition, and FOXM1 ChIP

    PMID:34545188

    Open questions at the time
    • Mechanism by which BubR1 biases NHEJ not resolved
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple post-translational marks (PLK1/CDK1 phosphorylation, SIRT2/CBP acetylation at K668/K250/K243, SUMO at K250) are integrated in time and space to coordinate checkpoint silencing, attachment maturation, and protein turnover remains unresolved.
  • No unified model integrating the modifications
  • Cross-talk between modifications and the two kinetochore pools undefined
  • In vivo substrate(s) of residual BubR1 catalytic activity unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3 GO:0016740 transferase activity 2
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1640170 Cell Cycle 4
Partners
ATMBUB3CDC20CENP-EMAD2PARP1PLK1PPP2R5A
Complex memberships
BubR1-CENP-E-microtubule ternary complexMitotic Checkpoint Complex (MCC)PP2A-B56

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 CENP-E directly activates BubR1 kinase activity at kinetochores using purified components and Xenopus egg extracts; 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 transducing linker that both activates and silences BubR1-dependent mitotic checkpoint signaling. In vitro reconstitution with purified BubR1, CENP-E, and microtubules; Xenopus egg extract immunodepletion and antibody-addition experiments Cell High 12859900
2005 Microtubule capture by CENP-E silences BubR1 kinase activity: a motorless fragment of CENP-E constitutively activates BubR1 at kinetochores producing checkpoint signaling not silenced by spindle capture or tension, whereas the motor domain of CENP-E silences BubR1 kinase in a ternary BubR1-CENP-E-microtubule complex in vitro. Biochemical reconstitution with purified BubR1, microtubules, and CENP-E; kinetochore-targeted motorless CENP-E fragment in cells The Journal of cell biology High 16144904
2012 PLK1 phosphorylates a conserved kinetochore attachment regulatory domain (KARD) in BUBR1, which then directly recruits PP2A-B56α phosphatase to kinetochores. This PP2A-B56α counters excessive Aurora B activity at kinetochores to stabilize kinetochore-microtubule attachments; removal of BUBR1 or PLK1 inhibition reduces PP2A-B56α kinetochore binding and elevates Aurora B substrate phosphorylation. Domain deletion and phospho-site mutagenesis; co-immunoprecipitation of BUBR1 with PP2A-B56α; Aurora B substrate phosphorylation assays; rescue experiments in mitotic cells Developmental cell High 23079597
2013 BubR1 directly binds the B56 family of PP2A regulatory subunits through a conserved motif phosphorylated by Cdk1 and Plk1; two conserved hydrophobic residues surrounding the Ser670 Cdk1 site are required for B56 binding. BubR1 targets a pool of B56-PP2A to kinetochores to counteract Aurora B kinase activity at improperly attached kinetochores. Direct binding assays; phospho-site mutagenesis; co-immunoprecipitation; kinetochore localization assays Journal of cell science High 23345399
2016 Crystal structure of the PP2A B56–BubR1 complex shows that a conserved BubR1 LxxIxE motif binds to the concave side of B56 pseudo-HEAT repeats (groove between repeats 3 and 4), distant from both the PP2A catalytic C subunit binding surface on B56 and the shugoshin-binding surface, allowing simultaneous binding. X-ray crystallography; biochemical binding assays Protein & cell High 27350047
2012 Vertebrate BUBR1 has evolved into an unusual pseudokinase: catalytic motifs are degenerate in many vertebrates, and putative catalysis by human BUBR1 is dispensable for error-free chromosome segregation, whereas residues that interact with ATP are essential for conformational stability. The ancestral KEN box was preserved while the kinase domain underwent parallel subfunctionalization across nine independent gene duplication events. Comparative genomic analysis; kinase-dead mutant complementation assays in human cells; structural analysis Developmental cell High 22698286
2012 BubR1 autophosphorylates itself in human cells in a CENP-E-dependent manner at unattached kinetochores; this autophosphorylation is required for full-strength mitotic checkpoint signaling and chromosome alignment. Expressing non-phosphorylatable BubR1 or depleting CENP-E causes metaphase chromosome misalignment and decreased Aurora B-mediated Ndc80 phosphorylation; phosphomimetic BubR1 rescues polar chromosomes in CENP-E-depleted cells. In vitro kinase assay; phospho-site mutagenesis; CENP-E depletion; live-cell imaging; kinetochore phosphorylation assays The Journal of cell biology High 22801780
2003 Aurora B kinase activity is required for kinetochore localization of BubR1, Mad2, and CENP-E; inhibition of Aurora B with ZM447439 prevents rebinding of BubR1 to metaphase kinetochores after reduction of centromeric tension and prevents Aurora B-mediated phosphorylation of BubR1 on entry into mitosis. BubR1 is also required for chromosome alignment independent of its spindle checkpoint role. Small molecule Aurora kinase inhibitor (ZM447439); RNAi knockdown; immunofluorescence; live-cell imaging The Journal of cell biology High 12719470
2004 BubR1 depletion in human cells prevents stable chromosome-spindle attachments; this can be rescued by Aurora kinase inhibition. BubR1 loss increases phosphorylation of the kinetochore-specific Aurora substrate CENP-A, indicating BubR1 links regulation of kinetochore-microtubule attachment stability to Aurora kinase activity. siRNA depletion; Aurora kinase inhibition; immunofluorescence; live-cell imaging; CENP-A phosphorylation assay Nature cell biology High 15592459
2010 Functional dissection of human BubR1 demonstrates that SAC and chromosome attachment functions are separable: mutation of five proline-directed serine phosphorylation sites abolishes chromosome attachment without affecting SAC; mutation of KEN boxes impairs SAC without affecting congression. The N-terminal KEN box (not the C-terminal) binds Cdc20; the GLEBS motif is strictly required for Bub3 interaction, kinetochore localization, and both SAC and congression functions. In vivo phospho-site identification by mass spectrometry; site-directed mutagenesis; co-immunoprecipitation; live-cell imaging; mitotic timing assays Journal of cell science High 20016069
2011 BUBR1 directly interacts with closed MAD2 (C-MAD2) through Arg133 and Gln134 of C-MAD2, and this BUBR1-C-MAD2 interaction is essential for MCC-mediated inhibition of APC/C. The same C-MAD2 residues are required for MAD2 dimerization and p31(comet) binding, suggesting the MAD2 αC helix is central to checkpoint activation and silencing. Co-immunoprecipitation; mutagenesis; in vitro APC/C inhibition assays The Journal of biological chemistry High 21525009
2014 BubR1 protein abundance declines with age due to decreased NAD+ levels and reduced SIRT2 deacetylase activity; SIRT2 maintains BubR1 by deacetylating lysine 668, which is counteracted by the acetyltransferase CBP. NMN treatment or SIRT2 overexpression restores BubR1 levels in vivo and extends median lifespan of BubR1 hypomorphic mice. SIRT2 overexpression mice; NMN treatment in vivo; acetylation-site mutagenesis; CBP identification; co-immunoprecipitation; lifespan analysis The EMBO journal High 24825348
2007 PLK1 phosphorylates BubR1 in vitro at two consensus Plk1 sites within the kinase domain during prometaphase; phosphomimetic BubR1 (2E) rescues chromosome alignment defects in BubR1-deficient cells, while unphosphorylatable BubR1 (2A) does not; phosphomimetic BubR1 also rescues alignment when Plk1 is co-depleted, placing PLK1-mediated BubR1 phosphorylation in the chromosome alignment pathway. In vitro kinase assay (Plk1 phosphorylates BubR1); siRNA depletion; phospho-mutant rescue experiments; co-immunoprecipitation The Journal of biological chemistry High 17376779
2007 BubR1 directly associates with APC (adenomatous polyposis coli) and EB1 in Xenopus egg extracts; using purified components BubR1 directly phosphorylates APC and forms a ternary complex with APC and microtubules; immunodepletion of BubR1 from extracts disrupts metaphase chromosome alignment, which requires BubR1 kinase activity. Co-immunoprecipitation; immunodepletion from Xenopus extracts; in vitro kinase assay with purified components; ternary complex formation assay The Journal of cell biology High 17709426
2011 BubR1 is sumoylated during mitotic progression; lysine 250 is the critical sumoylation site; expression of a sumoylation-deficient BubR1 K250R mutant induces chromosomal missegregation and mitotic delay, demonstrating that sumoylation at K250 is essential for BubR1 function in mitosis. Ectopic expression; SUMO pulldown; mutagenesis (K250R); immunofluorescence; mitotic timing assays The Journal of biological chemistry Medium 22167194
2017 The BubR1 loop region (distinct from the Bub1 loop) is essential for SAC function; BubR1 loop mutants bind Bub3 and are incorporated into MCC in vitro but have reduced ability to inhibit APC/C, suggesting BubR1:Bub3 requires phosphorylation to recognize and inhibit APC/C — directing Bub3 to distinct phosphorylated targets compared to Bub1. In vitro APC/C inhibition assay; MCC assembly assay; mutagenesis; SAC functional assays in cells Current biology : CB High 28943088
2016 Two distinct pools of BubR1/Bub3 exist at kinetochores: the major pool depends on direct Bub1/Bub3 binding and is required for chromosome alignment but not SAC; a separate pool binds directly to phosphorylated MELT repeats on KNL1 and is required for efficient incorporation into checkpoint complexes and robust SAC signaling. Defined BubR1/Bub3 binding mutants; kinetochore localization assays; SAC functional assays; co-immunoprecipitation Nature communications High 27457023
2009 In Drosophila, BubR1 kinase activity is required for spindle function (kinetochore fiber organization) but is dispensable for SAC function; the N-terminal KEN box is required for SAC but not spindle function; these two functions are substantially separable from each other and from mitotic timing. Kinase-dead and KEN-box mutant transgenic Drosophila; genetic epistasis with mad2; chromosome segregation analysis; spindle imaging The Journal of cell biology High 19951912
2015 In Drosophila, Bub3-BubR1 complex localizes to broken chromosome fragments (DNA double-strand breaks) in a Bub3-dependent manner; Cdc20 accumulates at DNA breaks in a BubR1 KEN-box-dependent manner; BubR1-dependent local APC/C inhibition around segregating broken chromosomes promotes their faithful segregation. RNAi depletion; KEN-box mutant analysis; APC/C activity biosensor; live-cell imaging; immunofluorescence The Journal of cell biology Medium 26553926
2017 SIRT2-dependent deacetylation of BubR1 at lysine 243 is required for normal meiotic spindle/chromosome organization in mouse oocytes; acetylation-mimetic BubR1-K243Q phenocopies Sirt2-knockdown meiotic defects, and non-acetylatable BubR1-K243R partly rescues meiotic deficits in Sirt2-depleted oocytes and suppresses spindle/chromosome anomalies in aged-mouse oocytes. Sirt2 depletion by morpholino/siRNA; acetylation-mimetic and non-acetylatable BubR1 mutant microinjection; spindle/chromosome immunofluorescence; aneuploidy scoring Aging cell Medium 29067790
2014 SIRT2 deacetylates BubR1 at lysine 250 both in vitro and in vivo; K250 acetylation during prometaphase inhibits APC/C-dependent proteolysis of BubR1 and regulates anaphase entry timing; SIRT2 knockdown increases BubR1 K250 acetylation. In vitro deacetylation assay; in vivo acetylation analysis; SIRT2 siRNA knockdown; Western blot of BubR1 levels and APC/C substrates Biochemical and biophysical research communications Medium 25285631
2005 BubR1 contains two distinct functional domains: the N-terminal region including the GLEBS motif is required for spindle checkpoint function through disruption of Bub3 binding; the C-terminal kinase domain is required for chromosome movement/alignment during prometaphase; a kinase-dead mutant prolongs mitosis, indicating the kinase domain regulates chromosome movement independently of the checkpoint. Deletion and kinase-dead point mutants; HeLa cell transfection; mitotic timing by live imaging; checkpoint assays with nocodazole Experimental cell research Medium 15907836
2020 The C-terminal basic helix of BubR1 is necessary (but not sufficient) for CENP-E interaction; a minimal acidic patch on the kinetochore-targeting domain of CENP-E is also essential. BubR1 is required for CENP-E recruitment to kinetochores, and this BubR1-CENP-E axis is critical for alignment of chromosomes that have failed other congression pathways. Domain mutagenesis; co-immunoprecipitation; kinetochore localization assays; chromosome alignment assays with rescue experiments Journal of cell science High 32665320
2005 BubR1 checkpoint function depends on both Bub1 kinase activity and Aurora B kinase activity in a redundant manner (two checkpoint arms converge on the MCC containing BubR1, Bub3, Mad2, Cdc20); MCC binding to APC/C requires an active checkpoint signal and depends on both Bub1 and Aurora B kinase activities. RNAi depletion of Bub1; Aurora kinase inhibitor ZM447439; co-immunoprecipitation of MCC-APC/C; mitotic arrest assays Journal of cell science Medium 16046481
2006 BubR1 physically interacts with PARP-1, identified by affinity pulldown and mass spectrometry and confirmed by reciprocal co-immunoprecipitation; BubR1 deficiency in MEFs compromises retention of intact PARP-1 after DNA damage, suggesting BubR1 participates in DNA damage responses through interaction with PARP-1. Affinity pulldown coupled with mass spectrometry; reciprocal co-immunoprecipitation; BubR1+/- mouse embryonic fibroblasts; DNA damage assays Oncogene Medium 16449973
2003 BCSG1 (breast cancer-specific gene 1/gamma-synuclein) physically associates with BubR1 in breast cancer cells (yeast two-hybrid, immunoprecipitation, GST pulldown); BCSG1 overexpression reduces BubR1 protein levels via the proteasome (prevented by MG-132), impairing mitotic checkpoint function. Yeast two-hybrid; co-immunoprecipitation; GST pulldown; proteasome inhibition with MG-132; Western blot Oncogene Medium 14576821
2007 hStaf/ZNF143 is required for BUB1B gene transcription; two conserved hStaf/ZNF143-binding sites in the BUB1B promoter are indispensable for promoter activity; CDE-CHR tandem elements in the promoter are essential for G2/M-specific cell-cycle-regulated transcription of BUB1B. Gel retardation assays; transient expression of mutant BUB1B promoter-reporter constructs; chromatin immunoprecipitation Nucleic acids research Medium 17478512
2005 BubR1 transcription is largely controlled by p53; in p53-null mouse cells, BubR1 expression is low and the checkpoint response to microtubule toxin is compromised; restoration of BubR1 in late-passage p53-/- cells restores checkpoint function and suppresses centrosome amplification. Microarray analysis; RT-PCR; Western blot; checkpoint assays in p53-/- cells with BubR1 re-expression Molecular and cellular biology Medium 15870277
2008 BubR1 haploinsufficiency causes premature sister-chromatid separation (PCS) in human cells; gradual reduction of BubR1 via shRNA reveals a dosage-dependent relationship: PCS is detected at all levels of reduction, whereas aneuploidy is clearly detected only when residual BubR1 is below 50%. Stable shRNA-transduced HeLa cells expressing gradient levels of BubR1; chromosome spreading; flow cytometry Human genetics Medium 18932004
2010 BubR1 localizes to kinetochores in mouse oocytes from GVBD to prometaphase I (co-localizing with PLK1) and redistributes away from kinetochores at metaphase I; spindle disruption relocalizes BubR1 to kinetochores. BubR1 depletion compromises kinetochore-microtubule attachments in meiosis I and abrogates the nocodazole-induced M I arrest. Immunofluorescence; BubR1 depletion by morpholino; dominant-negative overexpression; live-cell imaging; nocodazole checkpoint assay Cell cycle (Georgetown, Tex.) Medium 20237433
2012 FOXM1 transcriptionally regulates BUB1B expression by binding to and activating the BUB1B promoter, as demonstrated by chromatin immunoprecipitation; the FOXM1/BUB1B pathway promotes tumor cell growth and survival in rhabdomyosarcoma. Chromatin immunoprecipitation; shRNA knockdown; in vivo tumor growth assays Cancer research Medium 23002205
2021 Phosphorylated ATM interacts with BUB1B/BUBR1 after ionizing radiation; cells with aberrant BUB1B expression dominantly exploit mutagenic NHEJ for DNA repair in an ATM-dependent manner; FOXM1 was identified as a transcription factor causing increased BUB1B expression in CRT-recurrent bladder cancer clones. Co-immunoprecipitation of phospho-ATM with BUB1B; CRISPR/Cas9 DNA repair pathway analysis; ATM inhibitor experiments; ChIP for FOXM1 Oncogene Medium 34545188

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 1052 12719470
1996 Yeast HOG1 MAP kinase cascade is regulated by a multistep phosphorelay mechanism in the SLN1-YPD1-SSK1 "two-component" osmosensor. Cell 722 8808622
2004 BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice. Nature genetics 619 15208629
2008 Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency. Nature cell biology 315 18516091
2004 The human mitotic checkpoint protein BubR1 regulates chromosome-spindle attachments. Nature cell biology 269 15592459
1998 Activation of the yeast SSK2 MAP kinase kinase kinase by the SSK1 two-component response regulator. The EMBO journal 249 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 221 23079597
2003 Activating and silencing the mitotic checkpoint through CENP-E-dependent activation/inactivation of BubR1. Cell 203 12859900
2012 Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan. Nature cell biology 201 23242215
2014 SIRT2 induces the checkpoint kinase BubR1 to increase lifespan. The EMBO journal 196 24825348
2010 BUB1 and BUBR1: multifaceted kinases of the cell cycle. Trends in biochemical sciences 180 20888775
2013 Direct binding between BubR1 and B56-PP2A phosphatase complexes regulate mitotic progression. Journal of cell science 174 23345399
2005 CENP-A is required for accurate chromosome segregation and sustained kinetochore association of BubR1. Molecular and cellular biology 164 15870271
2003 BUBR1 deficiency results in abnormal megakaryopoiesis. Blood 155 14576056
2005 Bub1 and aurora B cooperate to maintain BubR1-mediated inhibition of APC/CCdc20. Journal of cell science 144 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 142 16411201
2003 Candida albicans response regulator gene SSK1 regulates a subset of genes whose functions are associated with cell wall biosynthesis and adaptation to oxidative stress. Eukaryotic cell 129 14555484
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
2011 Bub1 and BubR1: at the interface between chromosome attachment and the spindle checkpoint. Molecular and cellular biology 96 21628528
2010 BubR1 is a spindle assembly checkpoint protein regulating meiotic cell cycle progression of mouse oocyte. Cell cycle (Georgetown, Tex.) 96 20237433
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 81 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
2000 Mutation and expression analysis of human BUB1 and BUB1B in aneuploid breast cancer cell lines. Cancer letters 75 10773412
2011 Combined expression of BUB1B, DLGAP5, and PINK1 as predictors of poor outcome in adrenocortical tumors: validation in a Brazilian cohort of adult and pediatric patients. European journal of endocrinology 73 22048964
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
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
2009 High expression of BUBR1 is one of the factors for inducing DNA aneuploidy and progression in gastric cancer. Cancer science 56 20132214
1999 The mouse mitotic checkpoint gene bub1b, a novel bub1 family member, is expressed in a cell cycle-dependent manner. Genomics 55 9889005
2008 Phosphorylated Ssk1 prevents unphosphorylated Ssk1 from activating the Ssk2 mitogen-activated protein kinase kinase kinase in the yeast high-osmolarity glycerol osmoregulatory pathway. Molecular and cellular biology 53 18573873
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
2021 BUB1B and circBUB1B_544aa aggravate multiple myeloma malignancy through evoking chromosomal instability. Signal transduction and targeted therapy 50 34620840
1999 Differential stabilities of phosphorylated response regulator domains reflect functional roles of the yeast osmoregulatory SLN1 and SSK1 proteins. Journal of bacteriology 49 9882653
2009 Separating the spindle, checkpoint, and timer functions of BubR1. The Journal of cell biology 48 19951912
2007 Genomic instability and increased expression of BUB1B and MAD2L1 genes in ductal breast carcinoma. Cancer letters 48 17498870
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
2011 BUBR1 and closed MAD2 (C-MAD2) interact directly to assemble a functional mitotic checkpoint complex. The Journal of biological chemistry 46 21525009
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
2020 The Two-Component Response Regulator Ssk1 and the Mitogen-Activated Protein Kinase Hog1 Control Antifungal Drug Resistance and Cell Wall Architecture of Candida auris. mSphere 41 33055262
2023 In Silico Insight to Identify Potential Inhibitors of BUB1B from Mushroom Bioactive Compounds to Prevent Breast Cancer Metastasis. Frontiers in bioscience (Landmark edition) 40 37525917
2017 Sirt2-BubR1 acetylation pathway mediates the effects of advanced maternal age on oocyte quality. Aging cell 40 29067790
2017 BubR1 Promotes Bub3-Dependent APC/C Inhibition during Spindle Assembly Checkpoint Signaling. Current biology : CB 39 28943088
2009 The clinicopathological significance of BUBR1 overexpression in hepatocellular carcinoma. Journal of clinical pathology 38 19861558
2021 BUB1B promotes extrahepatic cholangiocarcinoma progression via JNK/c-Jun pathways. Cell death & disease 36 33431813
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
2021 Increased BUB1B/BUBR1 expression contributes to aberrant DNA repair activity leading to resistance to DNA-damaging agents. Oncogene 34 34545188
2017 Age-related decline in BubR1 impairs adult hippocampal neurogenesis. Aging cell 34 28383136
2013 BUB1 and BUBR1 inhibition decreases proliferation and colony formation, and enhances radiation sensitivity in pediatric glioblastoma cells. Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery 34 23728478
2013 New insights into the role of BubR1 in mitosis and beyond. International review of cell and molecular biology 34 24016527
2020 Spindle assembly checkpoint gene BUB1B is essential in breast cancer cell survival. Breast cancer research and treatment 33 33130993
2005 Deletion of the SSK1 response regulator gene in Candida albicans contributes to enhanced killing by human polymorphonuclear neutrophils. Infection and immunity 32 15664927
2017 Sensitivity to BUB1B Inhibition Defines an Alternative Classification of Glioblastoma. Cancer research 31 28855212
2022 BUB1B (BUB1 Mitotic Checkpoint Serine/Threonine Kinase B) promotes lung adenocarcinoma by interacting with Zinc Finger Protein ZNF143 and regulating glycolysis. Bioengineered 30 35068350
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
2011 BubR1 is modified by sumoylation during mitotic progression. The Journal of biological chemistry 30 22167194
2005 Comparative genomic hybridization and BUB1B mutation analyses in childhood cancers associated with mosaic variegated aneuploidy syndrome. Cancer letters 29 16182441
2013 Expression profiling of 519 kinase genes in matched malignant peripheral nerve sheath tumor/plexiform neurofibroma samples is discriminatory and identifies mitotic regulators BUB1B, PBK and NEK2 as overexpressed with transformation. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 28 23370767
2007 BubR1 and CENP-E have antagonistic effects upon the stability of microtubule-kinetochore attachments in Drosophila S2 cell mitosis. Cell cycle (Georgetown, Tex.) 28 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
2020 BUB1B Promotes Proliferation of Prostate Cancer via Transcriptional Regulation of MELK. Anti-cancer agents in medicinal chemistry 24 31893996
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
2014 Deacetylation of the mitotic checkpoint protein BubR1 at lysine 250 by SIRT2 and subsequent effects on BubR1 degradation during the prometaphase/anaphase transition. Biochemical and biophysical research communications 24 25285631
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
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
2008 Gradual reduction of BUBR1 protein levels results in premature sister-chromatid separation then in aneuploidy. Human genetics 21 18932004
2013 BubR1 is frequently repressed in acute myeloid leukemia and its re-expression sensitizes cells to antimitotic therapy. Haematologica 20 23812934
2010 BUBR1 expression in benign oral lesions and squamous cell carcinomas: correlation with human papillomavirus. Oncology reports 20 20204288
2002 The promoter region of the human BUBR1 gene and its expression analysis in lung cancer. Lung cancer (Amsterdam, Netherlands) 20 12445743
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
2020 Rare deleterious BUB1B variants induce premature ovarian insufficiency and early menopause. Human molecular genetics 18 32716490
2019 sFRP3 inhibition improves age-related cellular changes in BubR1 progeroid mice. Aging cell 17 30609266
2016 BubR1 alterations that reinforce mitotic surveillance act against aneuploidy and cancer. eLife 17 27528194
2014 How chromosome mis-segregation leads to cancer: lessons from BubR1 mouse models. Molecules and cells 16 25256220

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