Affinage

BUB1

Mitotic checkpoint serine/threonine-protein kinase BUB1 · UniProt O43683

Length
1085 aa
Mass
122.4 kDa
Annotated
2026-06-09
100 papers in source corpus 51 papers cited in narrative 51 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

BUB1 is a conserved serine/threonine protein kinase that acts as a master scaffold and signaling hub at the kinetochore, integrating spindle assembly checkpoint (SAC) control with chromosome biorientation (PMID:7969164, PMID:17389228). It is recruited to kinetochores when Mps1 phosphorylates MELT motifs on the KNL1/Spc105 scaffold, which engages the BUB1-bound BUB3 to dock the complex (PMID:22521787, PMID:22521786, PMID:25611342); BUB3 binding maps to the same BUB1 region required for kinetochore localization (PMID:9660858). Once positioned, BUB1 phosphorylates histone H2A (T120/T121 in higher eukaryotes, S121 in fission yeast) to create a centromeric mark that recruits shugoshin and concentrates the chromosomal passenger complex/Aurora B at the inner centromere (PMID:19965387, PMID:23209306, PMID:17389228), with autophosphorylation at the P+1 loop activating its kinase toward H2A but not Cdc20 (PMID:25308863). BUB1 functionally separates into a kinase arm dedicated to error correction and chromosome alignment and a scaffolding arm required for the SAC: its N-terminal TPR domain directly recruits BubR1 through heterodimerization, and a conserved CD1 region, phosphorylated by Mps1, binds Mad1 to assemble the Mad1-Mad2 platform that catalyzes mitotic checkpoint complex (MCC) formation (PMID:31257143, PMID:24402315, PMID:34013668, PMID:36289199). In parallel with MCC assembly, BUB1 directly phosphorylates Cdc20 and scaffolds Plk1-mediated Cdc20 phosphorylation to inhibit the APC/C (PMID:26912231), and serves as a principal kinetochore receptor for PLK1 following CDK1 priming (PMID:33248027). BUB1 abundance is reset after mitotic exit through APC/C-Cdh1-mediated, KEN-box-dependent degradation (PMID:17158872). Beyond mitosis, BUB1 kinase activity promotes TGF-β receptor heterodimerization and SMAD signaling (PMID:25564677) and supports telomere replication by phosphorylating TRF1 to recruit BLM helicase (PMID:29727616). Biallelic germline BUB1 mutations that reduce protein level and kinase activity cause microcephaly and intellectual disability with aneuploidy and cohesion defects (PMID:35044816).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1994 High

    Established BUB1 as a bona fide protein kinase physically and functionally coupled to Bub3, defining the founding biochemical unit of the checkpoint.

    Evidence In vitro kinase assay, immunoprecipitation and genetic epistasis in budding yeast

    PMID:7969164

    Open questions at the time
    • No physiological substrate identified beyond autophosphorylation and Bub3
    • Kinetochore recruitment mechanism unknown
  2. 1998 High

    Showed that Bub3 binding directs BUB1 to kinetochores and that BUB1 localizes to the centromere/kinetochore as a functional checkpoint component.

    Evidence Co-IP, deletion mapping, immunofluorescence and antibody electroporation in mammalian cells

    PMID:9660858 PMID:9790499 PMID:9914370

    Open questions at the time
    • Molecular receptor on the kinetochore not defined
    • Role of kinase activity vs scaffolding unresolved
  3. 2001 High

    Dissected BUB1's contribution to checkpoint establishment and revealed it as a tension/attachment-sensing node, while showing in egg extracts that kinase activity is dispensable for the core checkpoint.

    Evidence Immunodepletion with wild-type/kinase-dead add-back in Xenopus extracts; Co-IP and drug-treatment localization in mammalian cells

    PMID:11274370 PMID:11402067 PMID:11792804

    Open questions at the time
    • Apparent dispensability of kinase activity conflicts with later kinase-dependent roles
    • Substrate-level mechanism not addressed
  4. 2001 High

    Connected BUB1 to meiotic regulation by placing it downstream of MAPK/p90Rsk and demonstrating kinase-dependent CSF arrest.

    Evidence In vitro p90Rsk phosphorylation, oocyte injection, MEK1 inhibition and kinase-dead add-back in Xenopus

    PMID:11231148 PMID:12123578

    Open questions at the time
    • Meiotic substrates of activated BUB1 not identified
    • Relationship to mitotic activation mechanism unclear
  5. 2004 High

    Defined a unidirectional recruitment hierarchy in human cells, with BUB1 required for kinetochore loading of multiple downstream factors, and showed enhanced activation improves checkpoint efficiency.

    Evidence RNAi with systematic localization readouts; chromatin kinase assay and MAPK-site mutagenesis in Xenopus

    PMID:15020684 PMID:15241477

    Open questions at the time
    • Direct versus indirect recruitment of downstream factors not separated
    • Kinase substrates underlying recruitment not yet defined
  6. 2005 High

    Established BUB1 and Aurora B as parallel checkpoint arms converging on MCC binding to APC/C, and showed BUB1 is essential for chromosome congression.

    Evidence RNAi, chemical inhibition (ZM447439), live imaging and MCC-APC/C Co-IP in human cells

    PMID:15933723 PMID:16046481

    Open questions at the time
    • Biochemical basis of MCC-APC/C engagement not resolved
    • Molecular link between the two arms unknown
  7. 2007 High

    Identified BUB1 kinase activity as the master organizer of the inner centromere, directing shugoshin and the CPC, separating this from the checkpoint.

    Evidence Immunodepletion/RNAi with kinase-dead rescue in Xenopus extracts and HeLa; budding yeast kinase-domain deletion

    PMID:17389228 PMID:18081426

    Open questions at the time
    • Direct kinase substrate creating the shugoshin docking site not yet identified
  8. 2008 High

    Provided the first structural view of the BUB1 kinase domain and showed BUB1 uses KEN-box docking outside the kinase domain to engage its substrate Cdc20.

    Evidence X-ray crystallography, kinase assays and KEN-box mutagenesis with checkpoint readout

    PMID:18995837

    Open questions at the time
    • Catalytic phosphorylation of Cdc20 not yet demonstrated functionally
    • Mechanism of substrate selection partial
  9. 2009 High

    Identified histone H2A-S121 as the direct BUB1 substrate that recruits shugoshin, defining the kinase's primary segregation function, while genetically separating kinase from alignment versus checkpoint roles.

    Evidence In vitro kinase assay, phospho-specific antibodies, H2A mutant and shugoshin tethering rescue in fission yeast; RNAi structure-function complementation in human cells

    PMID:19487456 PMID:19965387

    Open questions at the time
    • How H2A phosphorylation is spatially restricted to centromeres not fully defined
  10. 2012 High

    Resolved the upstream recruitment logic by establishing Mps1-phosphorylated MELT motifs on KNL1/Spc105 as the BUB1 docking signal, and confirmed H2A-T121 as the in vivo substrate controlling Aurora B in mice.

    Evidence Kinetochore particle kinase assays, MELT-motif mutagenesis in budding/fission yeast; kinase-dead knock-in mouse phenotyping

    PMID:22365852 PMID:22521786 PMID:22521787 PMID:23209306

    Open questions at the time
    • Kinase-dead mice show aneuploidy without tumors, decoupling kinase from tumor suppression
  11. 2014 High

    Defined the CD1-Mad1 axis as the mechanism for Mad1 kinetochore recruitment and showed P+1 loop autophosphorylation activates BUB1 selectively toward H2A.

    Evidence In vitro Bub1-Mad1 reconstitution and kinetochore tethering bypass in budding yeast; crystallography and substrate-specific kinase assays in human cells

    PMID:24402315 PMID:25308863

    Open questions at the time
    • Stoichiometry and phospho-dependence of Mad1 binding not yet defined at atomic detail
  12. 2015 High

    Mapped BUB1's modular scaffolding: MELT-phospho/Bub3 binding, direct BubR1 heterodimerization, RZZ recruitment, ABBA/KEN-mediated Cdc20 capture, and autophosphorylation-controlled kinetochore turnover that spatially focuses H2A phosphorylation.

    Evidence In vitro phospho-MELT binding, domain swapping, RNAi complementation, phosphoproteomics, FRAP and tethering rescue in human cells

    PMID:25611342 PMID:26031201 PMID:26148513 PMID:26399325

    Open questions at the time
    • Conflicting reports on whether BubR1/Bub3 recruitment by BUB1 is required for SAC
    • Relative weighting of scaffolding modules context-dependent
  13. 2016 High

    Demonstrated a parallel APC/C-inhibitory output in which BUB1 directly phosphorylates Cdc20 and scaffolds Plk1-mediated Cdc20 phosphorylation independent of MCC assembly, and used selective inhibitors to isolate catalytic from scaffolding functions.

    Evidence In vitro kinase and APC/C inhibition assays, RNAi epistasis, phosphomimetic rescue; selective inhibitors BAY-320/BAY-524

    PMID:26885717 PMID:26912231

    Open questions at the time
    • In vivo contribution of Cdc20 phosphorylation relative to MCC not quantified
  14. 2018 High

    Defined the division of labor between BUB1/KNL1 and RZZ in Mad1-Mad2 activation, and uncovered non-mitotic roles of BUB1 in telomere replication via TRF1 phosphorylation and BLM recruitment.

    Evidence CRISPR editing and RNAi with SAC functional dissection; ChIP, in vitro TRF1 kinase assay, kinase-dead mutant and telomere FISH

    PMID:29727616 PMID:30415700

    Open questions at the time
    • Coordination of telomeric and mitotic BUB1 pools unclear
    • Compensatory splicing complicates loss-of-function interpretation
  15. 2019 High

    Showed integrated BUB1-RZZ cooperation in proximity-dependent Mad1 activation and reaffirmed a catalytic, Mad1-localization-independent checkpoint contribution; TPR domain shown necessary and sufficient to recruit BubR1/Mad3 to build the MCC platform.

    Evidence CRISPR/RNAi, proximity ligation, tethering bypass in human cells; conditional dimerization and domain mapping in budding/fission yeast

    PMID:30782962 PMID:31257143

    Open questions at the time
    • Nature of the residual catalytic checkpoint role not defined
  16. 2020 High

    Identified BUB1 (with CENP-U) as a principal PLK1 kinetochore receptor requiring CDK1 priming, and showed Haspin and BUB1 act redundantly to localize Aurora B for error correction.

    Evidence In vitro BUB1-PLK1 reconstitution, ectopic localization and docking-motif mutagenesis; dual Haspin/BUB1 inhibition with substrate readouts; RNAi/CRISPR redundancy analysis

    PMID:32027339 PMID:33248027 PMID:34551298

    Open questions at the time
    • Quantitative partitioning of PLK1 between BUB1 and CENP-U pools unresolved
  17. 2021 High

    Resolved the structural and catalytic logic of MCC platform assembly, showing Aurora B phosphorylation of BUB1 promotes MCC production and that BUB1 phospho-CD1 docks the Mad1 CTD, while extending BUB1 signaling to STAT3 phosphorylation in cancer.

    Evidence eSAC dimerization in yeast and human cells; high-resolution crystallography, NMR and ITC of Mad1-Bub1; Co-IP, kinase-dead and inhibitor STAT3 studies

    PMID:34013668 PMID:34852826 PMID:34861183

    Open questions at the time
    • Single-lab STAT3 link not independently confirmed
    • Integration of Aurora B input with Mps1 licensing partially defined
  18. 2022 High

    Completed the catalytic mechanism of MCC assembly via the Mad1 CTD-Cdc20 interface and linked BUB1 loss-of-function to a human Mendelian disorder.

    Evidence Crystal structure, XL-MS and in vitro MCC assembly; patient-derived cell analysis with localization, imaging and cohesion assays

    PMID:35044816 PMID:36289199

    Open questions at the time
    • Patient-cell findings from single laboratory
    • Tissue specificity of neurodevelopmental phenotype not mechanistically explained

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BUB1's mitotic, meiotic, telomeric, TGF-β, and STAT3 functions are coordinated within a cell, and the relative in vivo contribution of its catalytic versus scaffolding roles to genome stability and tumor suppression, remains unresolved.
  • No unified model linking mitotic and non-mitotic BUB1 activities
  • Decoupling of kinase activity from tumor suppression in mice not explained
  • Therapeutic window of BUB1 kinase inhibition not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016740 transferase activity 4 GO:0060090 molecular adaptor activity 4 GO:0042393 histone binding 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0000228 nuclear chromosome 4 GO:0005634 nucleus 1
Pathway
R-HSA-1640170 Cell Cycle 5 R-HSA-162582 Signal Transduction 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-73894 DNA Repair 2
Partners
BUB3BUBR1CDC20KNL1MAD1PLK1TGFBR1TRF1
Complex memberships
BUB1-BUB3 complexkinetochoremitotic checkpoint complex (MCC) signaling platform

Evidence

Reading pass · 51 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 Budding yeast Bub1 encodes a novel protein kinase: it autophosphorylates and phosphorylates Bub3 in vitro, physically associates with Bub3 by immunoprecipitation, and localizes to the nucleus. Bub1 and Bub3 are mutually dependent for function by genetic evidence. In vitro kinase assay, immunoprecipitation, genetic epistasis, sequence analysis Molecular and cellular biology High 7969164
1998 Human Bub3 is required for kinetochore localization of Bub1; Bub1 and Bub3 interact in mammalian cells, and deletion mapping identified the Bub1 domain required for Bub3 binding as identical to the domain required for kinetochore localization, indicating Bub3 recruits Bub1 to kinetochores. Both Bub1 and hBubR1 (BUB1B) independently bind Bub3. Co-immunoprecipitation, deletion mapping, immunofluorescence localization The Journal of cell biology High 9660858
1998 Human Bub1 (hBUB1) colocalizes with the centromere/kinetochore marker CREST during interphase, mitotic prophase, and nocodazole treatment; antibody electroporation experiments establish hBub1 as a functional component of the spindle checkpoint pathway. Immunofluorescence, antibody electroporation/functional assay Cell growth & differentiation Medium 9790499
1998 hBUB1 and hBUBR1 sequentially assemble at kinetochores during prophase; immunoelectron microscopy places hBUBR1 at the outer kinetochore plate, and both kinases colocalize with CENP-E, positioning them near the kinetochore surface where kinetochore–microtubule interactions are monitored. Immunofluorescence, immunoelectron microscopy, chromosome spreads Chromosoma Medium 9914370
1999 Drosophila Bub1 localizes to centromeres/kinetochores of unaligned chromosomes; Bub1 kinase activity is required for 3F3/2 epitope dephosphorylation at metaphase but not for 3F3/2 phosphorylation at prophase/prometaphase; Bub1 kinetochore localization is independent of zw10, rod, polo, or fizzy gene products. Immunofluorescence, genetic loss-of-function (P-element mutations), epistasis with kinetochore assembly mutants The Journal of cell biology Medium 10402457
2001 Xenopus Bub1 is essential for spindle checkpoint establishment and maintenance; immunodepletion abolishes the checkpoint and kinetochore binding of Mad1, Mad2, Bub3, and CENP-E; reintroduction of either wild-type or kinase-dead Bub1 restores the checkpoint and kinetochore localization of these proteins, demonstrating that Bub1 kinase activity is not required for spindle checkpoint function in Xenopus egg extracts. Immunodepletion, add-back reconstitution with wild-type and kinase-dead Bub1, immunofluorescence The Journal of cell biology High 11402067
2001 In mammalian cells, Bub1 and BubR1 are part of a common complex during mitosis. Bub1 localizes asymmetrically to kinetochores in a manner sensitive to both microtubule attachment and tension; Bub1 is rapidly phosphorylated following nocodazole or taxol treatment, whereas BubR1 phosphorylation is largely constitutive, indicating different regulatory inputs. Co-immunoprecipitation, immunofluorescence, phosphorylation analysis with drug treatments Journal of cell science Medium 11792804
2001 In response to low-dose vinblastine (tension loss), Bub1 and BubR1 are recruited to kinetochores but Mad2 is not; Mad2 does not associate with Bub1 or BubR1 in complex, while Mad2 does form a complex with Cdc20. This places Bub1/BubR1 in a tension-sensing arm distinct from the Mad2/Cdc20 attachment-sensing arm. Immunofluorescence with drug treatments, co-immunoprecipitation Proceedings of the National Academy of Sciences of the United States of America Medium 11274370
2001 Bub1 is activated during Xenopus oocyte meiosis in a MAPK-dependent manner; purified p90Rsk phosphorylates Bub1 in vitro and increases Bub1 kinase activity; injection of constitutively active p90Rsk restores Bub1 activation when MEK1 is inhibited, placing Bub1 downstream of the MAPK/Rsk pathway. In vitro kinase assay, oocyte injection, MEK1 inhibitor treatment, immunoprecipitation-kinase assay Current biology : CB High 11231148
2002 Immunodepletion of Bub1 from Xenopus egg extracts blocks Mos-induced CSF arrest; arrest is restored by wild-type but not kinase-dead Bub1, demonstrating that Bub1 kinase activity is required for establishing CSF metaphase arrest downstream of MAPK/Rsk, and that this pathway inhibits APC/C activation. Immunodepletion, add-back with kinase-dead mutant, Xenopus egg extract CSF arrest assay Current biology : CB High 12123578
2004 Human Bub1 is required for kinetochore localization of BubR1, CENP-E, CENP-F, and Mad2, as established by RNAi-mediated depletion in somatic cells; conversely, BubR1 depletion does not affect Bub1 kinetochore localization, establishing a unidirectional dependency. Bub1 depletion also increases lagging chromosomes, indicating a role in chromosome congression. RNA interference, immunofluorescence localization of checkpoint proteins Journal of cell science High 15020684
2004 Xenopus Bub1 becomes hyperphosphorylated and kinase-activated on unattached chromosomes; MAPK contributes to this activation; Bub1 without MAPK phosphorylation sites (Bub1-5AV) or kinase domain supports checkpoint under optimal conditions but is compromised at low kinetochore or drug concentrations and recruits other checkpoint proteins less efficiently, indicating that activation of Bub1 at kinetochores enhances checkpoint efficiency. Chromatin kinase assay, MAPK site mutagenesis, checkpoint rescue assay in Xenopus extracts, immunofluorescence The EMBO journal High 15241477
2005 Human Bub1 is essential for spindle checkpoint signaling and for correct chromosome congression; Bub1 depletion leads to misaligned chromatids with abnormal kinetochore–microtubule attachments; Bub1 and Aurora B are recruited to kinetochores independently and have additive effects when co-depleted, indicating parallel pathways. Live-cell imaging, RNA interference, double depletion epistasis The EMBO journal High 15933723
2005 Bub1 and Aurora B kinase form two parallel arms of the spindle checkpoint: depletion of Bub1 renders mitotic arrest dependent on Aurora B activity, and vice versa. Both arms converge on the mitotic checkpoint complex (MCC: BubR1, Bub3, Mad2, Cdc20), and both Bub1 and Aurora B kinase activity are required for MCC binding to APC/C when the checkpoint is active. RNAi, chemical inhibition (ZM447439), co-immunoprecipitation of MCC-APC/C complexes Journal of cell science High 16046481
2006 Bub1 is degraded during mitotic exit via APC/C-Cdh1; two KEN-box motifs on Bub1 are required for its ubiquitination by APC/C(Cdh1) in vitro and for its degradation in vivo; Cdh1 overexpression reduces Bub1 levels while Cdh1 RNAi depletion stabilizes Bub1. In vitro ubiquitination assay with immunopurified APC/C, RNAi, KEN-box mutagenesis, protein stability assay The Journal of biological chemistry High 17158872
2007 Bub1 kinase activity is required for directing Sgo1 to the inner centromere in budding yeast; bub1ΔK cells mislocalize Sgo1, show significant chromosome mis-segregation after nocodazole arrest/release, and can still arrest in response to microtubule-depolymerizing agents, separating checkpoint and chromosome biorientation functions. Genetic deletion of Bub1 kinase domain, immunofluorescence of Sgo1, chromosome segregation assays PLoS genetics High 18081426
2007 Bub1 acts as a master organizer of the inner centromeric region (ICR): Bub1 depletion from Xenopus egg extracts and HeLa cells displaces the chromosomal passenger complex (CPC) from the ICR and prevents centromere-restricted loading of Sgo; soluble Bub1 controls Sgo chromatin binding while CPC restricts it to centromeres; Bub1 kinase activity is pivotal for recruitment of all these components. Immunodepletion in Xenopus extracts, RNAi in HeLa cells, immunofluorescence, kinase-dead mutant rescue The Journal of cell biology High 17389228
2009 Bub1 phosphorylates the conserved serine 121 of histone H2A in fission yeast; this H2A-pS121 mark is required for centromeric localization of shugoshin proteins; the h2a-SA mutant phenocopies the bub1 kinase-dead mutant, and artificial centromere tethering of shugoshin rescues CIN defects of both mutants, establishing that the primary function of Bub1 kinase in chromosome segregation is to create an H2A phosphorylation mark that recruits shugoshin. In vitro kinase assay, phospho-specific antibodies, H2A-S121A mutant phenotypic analysis, shugoshin artificial tethering rescue Science (New York, N.Y.) High 19965387
2008 Crystal structure of the human Bub1 kinase domain reveals that the N-terminal extension is required for kinase activity; the activation segment is ordered but the C-terminal portion sterically restricts substrate access; Bub1 uses KEN-box docking motifs outside the kinase domain to recruit its substrate Cdc20; these KEN boxes are required for spindle checkpoint function in human cells. X-ray crystallography, kinase activity assays, KEN-box mutagenesis, spindle checkpoint assay Molecular cell High 18995837
2009 Bub1 can regulate chromosome segregation in a kinetochore-independent manner; Bub1 kinase activity is crucial for chromosome alignment but plays only a minor role in spindle checkpoint signaling; a conserved motif (amino acids 458–476) is essential for spindle checkpoint signaling but not chromosome alignment, dissecting the two functions. RNAi complementation with structural Bub1 mutants, isogenic HeLa and RPE1 cell lines, live-cell imaging The Journal of cell biology High 19487456
2010 Bub1 and CENP-F interact with KSHV latency-associated nuclear antigen LANA at kinetochores; Bub1 forms a complex with LANA that colocalizes with KSHV episomes tethered to host chromosomes; Bub1 knockdown by shRNA dramatically reduces KSHV genome copy number, indicating Bub1 is required for KSHV episome persistence during cell division. Co-immunoprecipitation, immunofluorescence, FISH, lentiviral shRNA knockdown with viral genome quantification Journal of virology Medium 20660191
2011 Bub1 overexpression in transgenic mice leads to near-diploid aneuploidy and tumor formation via aberrant Aurora B kinase hyperactivation; pharmacological or genetic (BubR1 overexpression) suppression of Aurora B activity largely corrects chromosome segregation errors caused by Bub1 overexpression, placing Aurora B downstream of elevated Bub1. Transgenic mouse model, chromosome segregation assays, Aurora B pharmacological inhibition, epistasis by BubR1 overexpression The Journal of cell biology High 21646403
2012 Mps1 kinase phosphorylates conserved MELT motifs on the kinetochore scaffold protein Spc105/KNL1; this phosphorylation recruits Bub1 to kinetochores; PP1 phosphatase reverses this modification; Spc105 mutants lacking Mps1 phosphorylation sites are defective in spindle checkpoint and growth. Kinetochore particle co-purification kinase assay, MELT-motif mutagenesis, genetic checkpoint assay, epistasis Current biology : CB High 22521787
2012 In fission yeast, Mph1 (Mps1) phosphorylates conserved MELT motifs in Spc7/KNL1 to recruit Bub1 and Bub3 to kinetochores; this recruitment is required to maintain the SAC signal. PP1 dephosphorylation of Spc7 antagonizes this recruitment. Biochemical phosphorylation analysis, MELT-motif mutagenesis, SAC functional assay Current biology : CB High 22521786
2012 Bub1 kinase activity controls Aurora B localization and activity through phosphorylation of histone H2A at threonine 121 (T121) in mice; Bub1 kinase-dead knock-in mice show substantial chromosome segregation errors and aneuploidy but unexpectedly do not develop increased spontaneous or carcinogen-induced tumors, separating Bub1 kinase-driven error correction from its tumor suppressor function. Kinase-dead knock-in mouse, chromosome segregation assays, tumorigenesis studies, H2A-T121 phosphorylation analysis The Journal of cell biology High 23209306
2012 Bub1 and Sgo1 modulate pericentric chromatin structure in response to altered microtubule dynamics in budding yeast; Bub1 kinase-mediated H2A-S121 phosphorylation and Sgo1 recruitment soften the chromatin spring and cause radial expansion of pericentric chromatin while reducing its dynamics, functioning as a rheostat for centromeric force balance. Fluorescence microscopy of chromatin dynamics, H2A phosphorylation assay, Sgo1 localization in bub1 mutants Current biology : CB Medium 22365852
2014 Mad1 kinetochore association in budding yeast is mediated by Mps1 phosphorylation of a region within Bub1 (conserved domain 1, CD1); tethering this Bub1 region to kinetochores bypasses Mps1-dependent checkpoint protein recruitment; the Mad1 interaction with Bub1 and kinetochores can be reconstituted in vitro in the presence of Mps1 and Mad2. In vitro reconstitution of Bub1-Mad1 interaction, kinetochore tethering bypass assay, Mps1 phosphorylation assays Genes & development High 24402315
2014 Phosphorylation of human Bub1 at the P+1 loop activates its kinase activity toward H2A but not Cdc20; crystal structure of phosphorylated Bub1 reveals phosphorylation-triggered reorganization of the P+1 loop; this activating phosphorylation occurs through intramolecular autophosphorylation and is constitutive during the cell cycle; enrichment of H2A-pT120 at mitotic kinetochores requires kinetochore targeting of Bub1. X-ray crystallography of phosphorylated Bub1, in vitro kinase assays with H2A and Cdc20 substrates, P+1 loop mutagenesis, immunofluorescence Structure (London, England : 1993) High 25308863
2014 BuGZ/ZNF207 binds to and stabilizes Bub3 through a GLEBS domain; BuGZ inhibition causes loss of both Bub3 and Bub1 from kinetochores, reduction of Bub1-dependent H2A phosphorylation at centromeres, attenuation of kinetochore-based Aurora B kinase activity, and lethal chromosome congression defects. RNAi screen, Co-IP, immunofluorescence, phospho-H2A antibody staining Developmental cell Medium 24462187
2015 Bub1, but not BubR1, enhances Bub3 binding to phosphorylated MELT motifs at kinetochores; BubR1 kinetochore localization depends 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 a functional checkpoint. In vitro binding assays with phospho-MELT peptides, domain swapping mutagenesis, kinetochore localization assays, checkpoint functional assay eLife High 25611342
2015 Human Bub1 contains a 50-amino-acid segment harboring an ABBA motif near a KEN box that is crucial for SAC signaling and efficient Cdc20 binding to kinetochores, but is not required for MAD1 kinetochore maintenance; BubR1 and Bub3 recruitment by Bub1 is dispensable for SAC activation in human cells. RNAi complementation with domain deletion mutants, immunofluorescence, checkpoint functional assays Journal of cell science Medium 26148513
2015 Bub1 middle region is required for kinetochore recruitment of the RZZ complex (not Zwint as previously proposed); a distinct Bub1 region mediates kinetochore localization of BubR1 through direct binding; removal of the BubR1-recruiting Bub1 region paradoxically increases checkpoint strength, indicating BubR1 localization through Bub1 has antagonistic checkpoint effects. RNAi, domain mapping, Co-IP, immunofluorescence, checkpoint functional assays Nature communications Medium 26031201
2015 Bub1 autophosphorylation at T589 regulates kinetochore turnover of Bub1; T589A mutation leads to uniform H2A-T120 phosphorylation along chromosome arms and aberrant Sgo1 recruitment, causing chromosome segregation errors; kinetochore tethering of Bub1-T589A refocuses H2A-T120 phosphorylation and Sgo1 to centromeres. Quantitative phosphoproteomics, Bub1 autophosphorylation site mutagenesis, FRAP, immunofluorescence, kinetochore-tethering rescue Nature communications High 26399325
2015 BUB1 interacts with TGF-β type I receptor (TGFBRI) in the presence of TGF-β and promotes heterodimerization of TGFBRI and TGFBRII; BUB1 also interacts with TGFBRII, suggesting a ternary complex; BUB1 kinase activity is required for SMAD3 recruitment to the receptor complex, SMAD2/SMAD3 phosphorylation, TGF-β-mediated EMT, migration, and invasion. RNAi screen, Co-immunoprecipitation, kinase-dead mutant, small-molecule inhibitor (2OH-BNPP1), in vivo xenograft phospho-SMAD2 analysis Science signaling High 25564677
2016 Bub1 directly phosphorylates Cdc20 and also scaffolds Plk1-mediated phosphorylation of Cdc20; Bub1–Plk1-dependent Cdc20 phosphorylation inhibits APC/C(Cdc20) in vitro, is required for spindle checkpoint signaling in human cells, is regulated by upstream checkpoint signals, and is dispensable for MCC assembly, constituting an APC/C-inhibitory mechanism parallel to MCC formation. In vitro kinase assay (Bub1 and Plk1 phosphorylation of Cdc20), APC/C inhibition assay, RNAi epistasis, phospho-mimetic Cdc20 rescue Nature communications High 26912231
2016 Selective small-molecule inhibitors of Bub1 kinase (BAY-320 and BAY-524) demonstrate that Bub1 kinase activity affects chromosome association of Shugoshin and the CPC but does not abolish global Aurora B function; kinase inhibition impairs chromosome arm resolution but has only minor effects on mitotic progression or SAC function; Bub1 kinase inhibition sensitizes cells to low-dose paclitaxel. In vitro kinase inhibitor characterization, cell-based phospho-H2A assay, Sgo1/CPC localization, live-cell imaging, proliferation assays eLife High 26885717
2017 In fission yeast meiosis, the meikin protein Moa1 recruits Polo-like kinase Plo1 to kinetochores; Plo1 then phosphorylates Spc7 (KNL1) to accumulate Bub1, causing persistent meiotic Bub1 kinetochore localization (in contrast to transient mitotic localization); this ensures robust Sgo1 localization and centromeric cohesion protection by cooperating with heterochromatin protein Swi6; the meiosis-specific Bub1 regulation is conserved in mouse. Genetic analysis, immunofluorescence of Bub1/Sgo1, phosphorylation analysis of Spc7, meiotic vs. mitotic comparison Genes to cells : devoted to molecular & cellular mechanisms Medium 28497540
2018 The BUB3-BUB1 complex binds to telomeres during S phase via TRF2-mediated targeting; BUB1 kinase activity and BUB3 telomere-binding ability are required for BUB3-BUB1 function at telomeres; BUB1 directly phosphorylates TRF1, and this promotes TRF1-mediated recruitment of BLM helicase to resolve replication stress; loss of BUB3-BUB1 causes fragile and shortened telomeres. ChIP, in vitro kinase assay (BUB1 phosphorylation of TRF1), Co-IP, kinase-dead mutant, telomere FISH/length assay Molecular cell High 29727616
2018 Genome-edited elimination of Bub1 in human cells shows that RZZ's sole role in SAC activation is to tether Mad1-Mad2 to kinetochores; in contrast, Bub1 and KNL1 activate kinetochore-bound Mad1-Mad2 to produce the 'wait anaphase' signal but are not required for fibrous corona formation; clonal BUB1-disrupted cells recover Bub1 expression via nonsense-associated alternative splicing. CRISPR genome editing, RNAi, immunofluorescence of SAC components, SAC functional assays Current biology : CB High 30415700
2018 BAY 1816032, a highly selective and orally bioavailable BUB1 kinase inhibitor, inhibits BUB1 signaling (H2A phosphorylation) in vitro and in cells; BUB1 kinase inhibition induces chromosome mis-segregation when combined with paclitaxel and is synergistic with taxanes, ATR inhibitors, and PARP inhibitors in cellular and xenograft models. In vitro kinase inhibitor assay, cell-based H2A phosphorylation assay, xenograft tumor models, combination drug assays Clinical cancer research Medium 30429199
2019 Efficient mitotic checkpoint signaling requires the integrated activities of Bub1 and the RZZ complex; Rod removal reduces the proximity of Bub1 and Mad1, and tethering Mad1 to kinetochores or increasing the Bub1-Mad1 interaction strength bypasses the requirement for Rod; Bub1 has Mad1-localization-independent checkpoint functions supported by low Bub1 levels, suggesting a catalytic role. CRISPR genome editing combined with RNAi, proximity ligation assay, kinetochore-tethering bypass experiments, checkpoint functional assays The EMBO journal High 30782962
2019 The N-terminal tetratricopeptide repeat (TPR) domain of Bub1 is both necessary and sufficient to directly bind and recruit Mad3 (BubR1); co-inducing dimerization of Mps1 with Bub1 triggers metaphase arrest dependent on Mad1, Mad2, and Mad3 even without kinetochores or KNL1/Spc105, establishing that Bub1-CD1 (binding Mad1) and Bub1-TPR (binding Mad3) together assemble the MCC signaling platform. Conditional heterodimerization (eSAC-like), domain deletion/mapping in budding and fission yeast, Co-IP, checkpoint functional assay Current biology : CB High 31257143
2020 BUB1 and CENP-U are the main PLK1 kinetochore receptors in mitosis; BUB1 recruits PLK1 to the outer kinetochore and CENP-U to the inner kinetochore; both share PP2A-docking and PLK1-docking motifs; CDK1 provides priming phosphorylation on BUB1 required for PLK1 docking; PLK1 also contributes to its own kinetochore recruitment through BUB1 and CENP-U. Ectopic localization assays, in vitro reconstitution of BUB1-PLK1 interaction, kinetochore localization studies, mutagenesis of docking motifs Molecular cell High 33248027
2020 Either Haspin or Bub1 kinase activity is independently sufficient to recruit Aurora B to a distinct chromosomal locus; joint inhibition of Haspin and Bub1 activities fully abolishes Aurora B accumulation at centromeres and impairs correction of erroneous KT-MT attachments but does not compromise the mitotic checkpoint nor phosphorylation of Aurora B kinetochore substrates Hec1, Dsn1, and Knl1. Combined chemical inhibition of Haspin and Bub1, immunofluorescence of Aurora B and substrates, chromosome segregation assays The Journal of cell biology High 32027339
2021 BUB1 directly interacts with STAT3 and phosphorylates STAT3 at Ser727; BUB1/STAT3 complex promotes transcription of STAT3 target genes; pharmacological BUB1 kinase inhibition (2OH-BNPP1) or kinase-domain mutation abrogates STAT3 Ser727 phosphorylation and STAT3 transcriptional activity in bladder cancer cells and in vivo xenografts. Co-immunoprecipitation, in vitro kinase assay (STAT3 Ser727 phosphorylation), kinase-dead mutant, small-molecule inhibitor, xenograft Journal of experimental & clinical cancer research Medium 34852826
2021 Aurora B kinase phosphorylates Bub1 to promote MCC production; conditional Aurora B dimerization with Bub1 (but not the KNL1 phosphodomain) produces ectopic MCC and mitotic arrest in budding yeast and human cells; this Aurora B input requires prior Mps1-dependent licensing of Bub1 kinetochore recruitment; Bub1 must recruit both Mad1 and Cdc20 for this ectopic signaling activity. Ectopic SAC activation (eSAC) dimerization system in budding yeast and HeLa cells, conditional heterodimerization, checkpoint functional assay Current biology : CB High 34861183
2021 Bub1 and CENP-U redundantly recruit Plk1 to kinetochores to stabilize kinetochore-microtubule attachments; depletion of Bub1 alone marginally affects chromosome segregation fidelity, but co-depletion of Bub1 and CENP-U causes significant mis-segregation; this redundancy is through Plk1 (not Aurora B), as confirmed by pharmacological epistasis. RNAi, CRISPR depletion, immunofluorescence of Plk1/Aurora B at kinetochores, pharmacological inhibitor epistasis, chromosome segregation assays Cell reports High 34551298
2021 Crystal structure of the Mad1 C-terminal domain bound to two phosphorylated Bub1 CD1 peptides at 1.75 Å resolution; Bub1 phospho-Thr461 directly contacts Mad1 Arg617 of the RLK motif and acts as an N-terminal helix dipole cap; in solution only one Bub1 CD1 peptide binds the Mad1 homodimer, reflecting asymmetry in the Mad1 coiled-coil. X-ray crystallography (1.75 Å), NMR, isothermal titration calorimetry EMBO reports High 34013668
2022 Mps1-mediated phosphorylation of Mad1 creates a phosphorylation-specific Mad1-Cdc20 interaction; together with Bub1-Mad1 association, this generates a tripartite assembly of Bub1 and Cdc20 onto Mad1 CTD that positions Cdc20 MIM near O-Mad2, catalyzing C-Mad2:Cdc20 formation and MCC assembly. Crystal structure of Mad1 CTD-Cdc20, cross-linking mass spectrometry, in vitro MCC assembly assay Nature communications High 36289199
2022 Biallelic BUB1 germline mutations in human patients cause microcephaly and intellectual disability; patient cells show reduced BUB1 protein and kinase activity; impaired kinase activity prohibits centromeric recruitment of Aurora B, SGO1, and TOP2A, correlating with anaphase bridges, aneuploidy, and defective sister chromatid cohesion; BUB1 levels mainly affect BUBR1 kinetochore recruitment. Patient-derived cell analysis, immunofluorescence of Aurora B/SGO1/TOP2A, live-cell imaging of mitosis, cohesion assays Science advances Medium 35044816
2011 ATM phosphorylates Bub1 on serine 314 in response to DNA damage in vivo; ATM-mediated Bub1 S314 phosphorylation is required for IR-induced Bub1 activation and Bub1-mediated H2A threonine 121 phosphorylation after ionizing radiation; Bub1 knockdown causes prolonged H2AX foci and DNA damage hypersensitivity. In vivo phosphorylation assay, S314 mutagenesis, IR treatment, H2AX foci assay, comet assay DNA repair Medium 22071147

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Phosphorylation of H2A by Bub1 prevents chromosomal instability through localizing shugoshin. Science (New York, N.Y.) 402 19965387
1998 The human homologue of Bub3 is required for kinetochore localization of Bub1 and a Mad3/Bub1-related protein kinase. The Journal of cell biology 376 9660858
2012 Phosphoregulation of Spc105 by Mps1 and PP1 regulates Bub1 localization to kinetochores. Current biology : CB 299 22521787
2004 Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and Mad2, and chromosome congression. Journal of cell science 288 15020684
2012 Phosphodependent recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 kinase maintains the spindle checkpoint. Current biology : CB 242 22521786
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
2001 Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity. The Journal of cell biology 196 11402067
1994 The Saccharomyces cerevisiae checkpoint gene BUB1 encodes a novel protein kinase. Molecular and cellular biology 188 7969164
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
2005 A dual role for Bub1 in the spindle checkpoint and chromosome congression. The EMBO journal 181 15933723
2010 BUB1 and BUBR1: multifaceted kinases of the cell cycle. Trends in biochemical sciences 180 20888775
2007 Bub1 mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis. The Journal of cell biology 180 17938250
1999 Mutations in the essential spindle checkpoint gene bub1 cause chromosome missegregation and fail to block apoptosis in Drosophila. The Journal of cell biology 177 10402457
2009 Bub1 regulates chromosome segregation in a kinetochore-independent manner. The Journal of cell biology 175 19487456
1998 The hBUB1 and hBUBR1 kinases sequentially assemble onto kinetochores during prophase with hBUBR1 concentrating at the kinetochore plates in mitosis. Chromosoma 161 9914370
2002 Genetic and epigenetic inactivation of mitotic checkpoint genes hBUB1 and hBUBR1 and their relationship to survival. Cancer research 160 11782350
2014 Mad1 kinetochore recruitment by Mps1-mediated phosphorylation of Bub1 signals the spindle checkpoint. Genes & development 159 24402315
2011 Bub1 overexpression induces aneuploidy and tumor formation through Aurora B kinase hyperactivation. The Journal of cell biology 158 21646403
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 144 16046481
2015 A molecular basis for the differential roles of Bub1 and BubR1 in the spindle assembly checkpoint. eLife 126 25611342
2007 Bub1 maintains centromeric cohesion by activation of the spindle checkpoint. Developmental cell 108 17925231
2007 Bub1 kinase targets Sgo1 to ensure efficient chromosome biorientation in budding yeast mitosis. PLoS genetics 97 18081426
2015 Distinct domains in Bub1 localize RZZ and BubR1 to kinetochores to regulate the checkpoint. Nature communications 96 26031201
2011 Bub1 and BubR1: at the interface between chromosome attachment and the spindle checkpoint. Molecular and cellular biology 96 21628528
2007 Bub1 is essential for assembly of the functional inner centromere. The Journal of cell biology 95 17389228
2016 The Bub1-Plk1 kinase complex promotes spindle checkpoint signalling through Cdc20 phosphorylation. Nature communications 93 26912231
2020 BUB1 and CENP-U, Primed by CDK1, Are the Main PLK1 Kinetochore Receptors in Mitosis. Molecular cell 91 33248027
2018 Distinct Roles of RZZ and Bub1-KNL1 in Mitotic Checkpoint Signaling and Kinetochore Expansion. Current biology : CB 89 30415700
2007 BUB1 mediation of caspase-independent mitotic death determines cell fate. The Journal of cell biology 89 17620410
2001 Molecular analyses of the mitotic checkpoint components hsMAD2, hBUB1 and hBUB3 in human cancer. International journal of cancer 86 11400114
1999 Mutational inactivation of mitotic checkpoint genes, hsMAD2 and hBUB1, is rare in sporadic digestive tract cancers. Japanese journal of cancer research : Gann 84 10543255
2012 Bub1 kinase activity drives error correction and mitotic checkpoint control but not tumor suppression. The Journal of cell biology 83 23209306
2008 Structure and substrate recruitment of the human spindle checkpoint kinase Bub1. Molecular cell 83 18995837
2001 Bub1 is activated by the protein kinase p90(Rsk) during Xenopus oocyte maturation. Current biology : CB 82 11231148
2002 The spindle checkpoint kinase bub1 and cyclin e/cdk2 both contribute to the establishment of meiotic metaphase arrest by cytostatic factor. Current biology : CB 80 12123578
2015 The kinase activity of the Ser/Thr kinase BUB1 promotes TGF-β signaling. Science signaling 78 25564677
2000 Mutation and expression analysis of human BUB1 and BUB1B in aneuploid breast cancer cell lines. Cancer letters 75 10773412
2000 Mutation analysis of mitotic checkpoint genes (hBUB1 and hBUBR1) and microsatellite instability in adult T-cell leukemia/lymphoma. Cancer letters 75 10960763
2000 Somatic mutation of the hBUB1 mitotic checkpoint gene in primary lung cancer. Genes, chromosomes & cancer 73 10992296
2020 Untangling the contribution of Haspin and Bub1 to Aurora B function during mitosis. The Journal of cell biology 72 32027339
2018 BUB1 Is Essential for the Viability of Human Cells in which the Spindle Assembly Checkpoint Is Compromised. Cell reports 72 29425499
2014 BuGZ is required for Bub3 stability, Bub1 kinetochore function, and chromosome alignment. Developmental cell 70 24462187
2008 Kinetochore-microtubule interactions "in check" by Bub1, Bub3 and BubR1: The dual task of attaching and signalling. Cell cycle (Georgetown, Tex.) 69 18594200
2015 Dissecting the roles of human BUB1 in the spindle assembly checkpoint. Journal of cell science 68 26148513
2006 KEN-box-dependent degradation of the Bub1 spindle checkpoint kinase by the anaphase-promoting complex/cyclosome. The Journal of biological chemistry 62 17158872
2004 Phosphorylation and activation of Bub1 on unattached chromosomes facilitate the spindle checkpoint. The EMBO journal 62 15241477
2018 Inhibition of BUB1 Kinase by BAY 1816032 Sensitizes Tumor Cells toward Taxanes, ATR, and PARP Inhibitors In Vitro and In Vivo. Clinical cancer research : an official journal of the American Association for Cancer Research 60 30429199
2006 Bub1 prevents chromosome misalignment and precocious anaphase during mouse oocyte meiosis. Cell cycle (Georgetown, Tex.) 59 16969117
2010 Bub1 and CENP-F can contribute to Kaposi's sarcoma-associated herpesvirus genome persistence by targeting LANA to kinetochores. Journal of virology 58 20660191
2000 Infrequent mutation of the hBUB1 and hBUBR1 genes in human lung cancer. Japanese journal of cancer research : Gann 58 10835495
1999 Mutation analysis of hBUB1 in aneuploid HNSCC and lung cancer cell lines. Cancer letters 58 10395177
2021 BUB1 drives the occurrence and development of bladder cancer by mediating the STAT3 signaling pathway. Journal of experimental & clinical cancer research : CR 57 34852826
2020 BUB1 promotes proliferation of liver cancer cells by activating SMAD2 phosphorylation. Oncology letters 56 32269624
2019 Efficient mitotic checkpoint signaling depends on integrated activities of Bub1 and the RZZ complex. The EMBO journal 56 30782962
2018 The BUB3-BUB1 Complex Promotes Telomere DNA Replication. Molecular cell 55 29727616
2016 Probing the catalytic functions of Bub1 kinase using the small molecule inhibitors BAY-320 and BAY-524. eLife 55 26885717
1999 The mouse mitotic checkpoint gene bub1b, a novel bub1 family member, is expressed in a cell cycle-dependent manner. Genomics 55 9889005
2009 Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice. Proceedings of the National Academy of Sciences of the United States of America 52 19617567
2005 Bub1 multitasking in mitosis. Cell cycle (Georgetown, Tex.) 51 15655378
2021 Bub1 kinase in the regulation of mitosis. Animal cells and systems 49 33717411
2002 hBUB1 defects in leukemia and lymphoma cells. Oncogene 48 12096343
2007 Surveillance mechanism linking Bub1 loss to the p53 pathway. Proceedings of the National Academy of Sciences of the United States of America 47 17488820
2011 The kinetochore protein Bub1 participates in the DNA damage response. DNA repair 46 22071147
2001 Expression of Bub1 gene correlates with tumor proliferating activity in human gastric carcinomas. Pathobiology : journal of immunopathology, molecular and cellular biology 46 11641614
2017 MiR-490-5p Suppresses Cell Proliferation and Invasion by Targeting BUB1 in Hepatocellular Carcinoma Cells. Pharmacology 44 28810242
2012 Bub1 kinase and Sgo1 modulate pericentric chromatin in response to altered microtubule dynamics. Current biology : CB 44 22365852
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
2011 Bub1, Sgo1, and Mps1 mediate a distinct pathway for chromosome biorientation in budding yeast. Molecular biology of the cell 40 21389114
2007 Bub1: escapades in a cellular world. Cell cycle (Georgetown, Tex.) 40 17643075
2004 Differential expression of the MAD2, BUB1 and HSP27 genes in Barrett's oesophagus-their association with aneuploidy and neoplastic progression. Mutation research 40 15013707
2021 Bub1 and CENP-U redundantly recruit Plk1 to stabilize kinetochore-microtubule attachments and ensure accurate chromosome segregation. Cell reports 36 34551298
2009 Bub1 and Bub3 promote the conversion from monopolar to bipolar chromosome attachment independently of shugoshin. EMBO reports 36 19680287
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
2004 Possible causes of chromosome instability: comparison of chromosomal abnormalities in cancer cell lines with mutations in BRCA1, BRCA2, CHK2 and BUB1. Cytogenetic and genome research 34 15162061
1998 Human Bub1: a putative spindle checkpoint kinase closely linked to cell proliferation. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 34 9790499
2001 Mitotic checkpoint genes hBUB1, hBUB1B, hBUB3 and TTK in human bladder cancer, screening for mutations and loss of heterozygosity. Carcinogenesis 33 11323402
2004 Expression of BUB1 protein in gastric cancer correlates with the histological subtype, but not with DNA ploidy or microsatellite instability. The Journal of pathology 31 14743503
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
2021 Aurora B phosphorylates Bub1 to promote spindle assembly checkpoint signaling. Current biology : CB 30 34861183
2017 Meikin-associated polo-like kinase specifies Bub1 distribution in meiosis I. Genes to cells : devoted to molecular & cellular mechanisms 30 28497540
1997 Mammalian BUB1 protein kinases: map positions and in vivo expression. Genomics 30 9441741
2022 Biallelic BUB1 mutations cause microcephaly, developmental delay, and variable effects on cohesion and chromosome segregation. Science advances 29 35044816
2021 Molecular mechanism of Mad1 kinetochore targeting by phosphorylated Bub1. EMBO reports 28 34013668
2014 Substrate-specific activation of the mitotic kinase Bub1 through intramolecular autophosphorylation and kinetochore targeting. Structure (London, England : 1993) 28 25308863
2021 Inhibition of BUB1 suppresses tumorigenesis of osteosarcoma via blocking of PI3K/Akt and ERK pathways. Journal of cellular and molecular medicine 27 34337852
2020 Aberrant BUB1 Overexpression Promotes Mitotic Segregation Errors and Chromosomal Instability in Multiple Myeloma. Cancers 26 32781708
2015 Bub1 autophosphorylation feeds back to regulate kinetochore docking and promote localized substrate phosphorylation. Nature communications 26 26399325
2022 The spindle checkpoint proteins BUB1 and BUBR1: (SLiM)ming down to the basics. Trends in biochemical sciences 25 35184951
2011 Aurora B hyperactivation by Bub1 overexpression promotes chromosome missegregation. Cell cycle (Georgetown, Tex.) 25 22033440
2014 BUB1 mRNA is significantly co-expressed with AURKA and AURKB mRNA in advanced-stage ovarian serous carcinoma. Virchows Archiv : an international journal of pathology 24 24756216
2010 BUB3 that dissociates from BUB1 activates caspase-independent mitotic death (CIMD). Cell death and differentiation 24 20057499
2001 Mutation analysis of hBUB1, hBUBR1 and hBUB3 genes in glioblastomas. Acta neuropathologica 24 11355300
2022 Juxtaposition of Bub1 and Cdc20 on phosphorylated Mad1 during catalytic mitotic checkpoint complex assembly. Nature communications 23 36289199
2015 Spindle Checkpoint Factors Bub1 and Bub2 Promote DNA Double-Strand Break Repair by Nonhomologous End Joining. Molecular and cellular biology 23 25963654
2012 MicroRNA-450a-3p represses cell proliferation and regulates embryo development by regulating Bub1 expression in mouse. PloS one 23 23110129
2022 BUB1 Is Identified as a Potential Therapeutic Target for Pancreatic Cancer Treatment. Frontiers in public health 22 35769782
2021 KIF4A knockdown suppresses ovarian cancer cell proliferation and induces apoptosis by downregulating BUB1 expression. Molecular medicine reports 22 34013367
2019 The Bub1-TPR Domain Interacts Directly with Mad3 to Generate Robust Spindle Checkpoint Arrest. Current biology : CB 22 31257143
2008 Overexpression of the mitotic spindle assembly checkpoint genes hBUB1, hBUBR1 and hMAD2 in thyroid carcinomas with aggressive nature. Anticancer research 22 18383837

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