Affinage

BUB3

Mitotic checkpoint protein BUB3 · UniProt O43684

Length
328 aa
Mass
37.2 kDa
Annotated
2026-04-28
81 papers in source corpus 38 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BUB3 is a WD40 β-propeller protein that functions as a central phospho-amino acid adaptor and scaffolding hub in the spindle assembly checkpoint (SAC) and has additional roles in telomere replication, DNA repair, and transcriptional regulation. Its seven-bladed β-propeller directly reads MPS1-phosphorylated MELT (and synergistic SHT) motifs on KNL1/SPC105, recruiting BUB1 and BubR1 kinases to unattached kinetochores via mutually exclusive binding of their GLEBS motifs along the propeller top surface; downstream, BUB3–BubR1 stimulates CDC20 engagement to assemble the mitotic checkpoint complex (MCC) that inhibits APC/C, and BubR1-loop–directed BUB3 recognition of phosphorylated APC/C targets is required for full inhibition (PMID:15544799, PMID:17227844, PMID:24066227, PMID:25661489, PMID:25246557, PMID:28943088). BUB3 protein levels are positively regulated by the BuGZ chaperone and USP7 deubiquitinase and negatively regulated by CRL4-RBBP7–mediated ubiquitination during mitotic exit; genetic loss causes embryonic lethality, checkpoint failure, and chromosome missegregation (PMID:10995385, PMID:24462186, PMID:25003721, PMID:31911655). Beyond mitosis, BUB3–BUB1 binds telomeres via TRF2 during S phase to promote telomere DNA replication, ATM phosphorylates BUB3 at Ser135 to dually regulate SAC activation and NHEJ repair, and BUB3 reads EZH2-catalyzed methylation on FOXA1 to recruit USP7 for FOXA1 stabilization (PMID:29727616, PMID:35085551, PMID:33827814).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1998 High

    Establishing BUB3 as a kinetochore-localized adaptor for BUB1 and BubR1 resolved how checkpoint kinases reach their site of action during prometaphase.

    Evidence Co-immunoprecipitation and deletion mapping in mammalian cells showed the BUB1 domain needed for BUB3 binding is the same required for kinetochore localization.

    PMID:9660858

    Open questions at the time
    • Structural basis of BUB3–BUB1 interaction unknown
    • Whether BUB3 is directly tethered to kinetochore scaffold not addressed
  2. 1999 High

    Reconstitution of a BUB3–BUB1 kinase complex in vitro demonstrated that BUB3 partners with an active kinase, and dynamic kinetochore localization tied BUB3 to microtubule-attachment sensing.

    Evidence Recombinant co-expression in insect cells yielded a complex with kinase activity; immunofluorescence showed BUB3 retained on unattached/lagging chromosomes.

    PMID:10411903

    Open questions at the time
    • Substrate of the BUB3–BUB1 kinase complex not identified
    • Signal that removes BUB3 from aligned chromosomes unknown
  3. 2000 High

    Knockout studies established BUB3 as essential for embryonic viability and spindle checkpoint function in vivo, demonstrating it is not redundant with other WD40 checkpoint proteins.

    Evidence Bub3-null mouse embryos die by E6.5–7.5 with mitotic errors and fail to arrest upon spindle poison challenge.

    PMID:10995385

    Open questions at the time
    • Cell-type-specific requirements not distinguished
    • Whether RAE1 partially compensates in heterozygotes tested later
  4. 2001 High

    Defining BUB3 as a WD40-dependent interaction platform for MAD2, MAD3/BubR1, and CDC20 revealed how the checkpoint complex is assembled, with BUB3–CDC20 association upregulated upon checkpoint activation.

    Evidence WD40 point mutagenesis in yeast disrupted interactions with MAD2, MAD3, and CDC20 and abolished checkpoint response.

    PMID:11726501

    Open questions at the time
    • Whether BUB3 contacts these partners simultaneously or sequentially unclear
    • Stoichiometry of the assembled complex undefined
  5. 2003 High

    Haploinsufficiency genetics revealed functional cooperation between BUB3 and the WD40 protein RAE1 in checkpoint maintenance, with RAE1 overexpression rescuing BUB3 haploinsufficiency.

    Evidence Bub3+/− and Rae1+/− mice showed additive checkpoint defects; RAE1 overexpression rescued both.

    PMID:12551952

    Open questions at the time
    • Molecular basis of RAE1–BUB3 functional overlap not defined
    • Whether these proteins share substrates unknown
  6. 2007 High

    Crystal structures of BUB3 bound to GLEBS-motif peptides from BUB1 and MAD3 defined how the β-propeller top surface engages checkpoint partners through mutually exclusive binding, with quantitative affinity (~5 µM) measured.

    Evidence X-ray crystallography of yeast BUB3–GLEBS complexes, ITC, and mutagenesis with checkpoint/chromosome stability assays.

    PMID:15544799 PMID:17227844

    Open questions at the time
    • Full-length complex structure not available
    • Whether post-translational modifications modulate affinity not tested
  7. 2008 High

    RNAi phenotyping revealed a checkpoint-independent role for BUB3 in establishing stable end-on kinetochore-microtubule attachments, separable from BubR1's role and Aurora B's error-correction pathway.

    Evidence BUB3 RNAi in human cells caused side-on attachment defects worsened by Aurora B inhibition.

    PMID:18199686

    Open questions at the time
    • Mechanism by which BUB3 promotes end-on attachment not identified
    • Whether this involves direct microtubule contacts unknown
  8. 2013 High

    Identification of BUB3 as the phospho-MELT reader on KNL1/SPC105 resolved the long-standing question of how MPS1 kinase activity is transduced into checkpoint protein recruitment at kinetochores.

    Evidence Crystal structure of BUB3–MELpT complex plus mutagenesis and checkpoint/kinetochore recruitment assays in cells.

    PMID:24066227

    Open questions at the time
    • Whether BUB3 directly senses the phospho-SHT motif remained untested
    • Contribution of individual KNL1 MELT repeats not dissected
  9. 2014 High

    Reconstitution of the MCC assembly pathway showed BUB3 acts at two stages — enhancing CDC20 recruitment at kinetochores and stimulating BubR1's N-terminal CDC20-binding domain to generate the final BUB3–BubR1–CDC20 inhibitor of APC/C.

    Evidence In vitro reconstitution and APC/C ubiquitination assays combined with cell-based complementation.

    PMID:25246557

    Open questions at the time
    • Kinetic parameters of BUB3's catalytic versus stoichiometric contribution not resolved
    • Structural basis of MCC–APC/C interaction involving BUB3 not defined
  10. 2014 High

    Discovery that BuGZ/ZNF207 stabilizes BUB3 and enhances its kinetochore loading explained how BUB3 protein levels and localization are positively regulated, while USP7 was identified as a deubiquitinase that stabilizes BUB3.

    Evidence Two independent studies showed BuGZ binds BUB3 via its GLEBS domain and promotes kinetochore loading; USP7 depletion reduced BUB3 levels and caused mitotic defects.

    PMID:24462186 PMID:24462187 PMID:25003721

    Open questions at the time
    • Whether BuGZ and USP7 act on the same or distinct pools of BUB3 unknown
    • Ubiquitin sites on BUB3 targeted by USP7 not identified
  11. 2015 High

    Identification of the phospho-SHT motif as a synergistic binding determinant for BUB3 on vertebrate KNL1 repeats revealed a two-step phosphorylation code read by BUB3's conserved surface.

    Evidence Systematic mutagenesis of KNL1 repeats plus in vitro binding and BUB3 interface mutagenesis with kinetochore localization assays.

    PMID:25661489

    Open questions at the time
    • Kinase responsible for SHT phosphorylation not definitively identified
    • Structural basis of dual MELpT–SHpT recognition not resolved
  12. 2017 High

    Demonstrating that BubR1-loop–directed BUB3 recognition of phosphorylated APC/C targets is required for full APC/C inhibition revealed that BUB3 functions as a phospho-reader not only at kinetochores but also in the cytoplasmic MCC–APC/C inhibitory step.

    Evidence In vitro MCC reconstitution with BubR1 loop mutants showed normal MCC formation but impaired APC/C inhibition.

    PMID:28943088

    Open questions at the time
    • Identity of the phosphorylated APC/C target recognized by BUB3–BubR1 unknown
    • Whether this recognition is conserved in yeast not tested
  13. 2018 High

    Discovery that BUB3–BUB1 binds telomeres via TRF2 during S phase and BUB1 phosphorylates TRF1 to recruit BLM helicase expanded BUB3's function beyond mitosis into telomere DNA replication.

    Evidence ChIP, co-immunoprecipitation, in vitro kinase assay, telomere FISH, and RNAi/knockout.

    PMID:29727616

    Open questions at the time
    • How BUB3 is specifically recruited to telomeres during S phase versus kinetochores during M phase unclear
    • Whether BUB3's phospho-reading activity is required at telomeres not tested
  14. 2020 High

    Identification of CRL4-RBBP7 as the E3 ligase that ubiquitinates BUB3 for degradation during mitotic exit provided the negative regulatory mechanism that terminates SAC signaling, with PML bodies protecting BUB3 during interphase.

    Evidence Co-IP, ubiquitination assays, RNAi, and mitotic exit timing in human cells.

    PMID:31911655

    Open questions at the time
    • Specific ubiquitinated lysines on BUB3 not mapped
    • How PML body association protects BUB3 mechanistically not defined
  15. 2021 High

    Demonstration that BUB3's WD40 domain reads EZH2-catalyzed lysine methylation on FOXA1 to recruit USP7 established BUB3 as a methyl-lysine reader acting outside the mitotic checkpoint, in transcription factor stabilization.

    Evidence Reconstituted methylation–recognition–deubiquitination cascade with mutagenesis in prostate cancer cells.

    PMID:33827814

    Open questions at the time
    • Whether BUB3 reads methylation on other substrates not explored
    • Structural basis of methyl-lysine recognition by BUB3 WD40 domain not determined
  16. 2022 High

    ATM-dependent phosphorylation of BUB3 at Ser135 revealed a dual-use modification that enhances SAC activation during mitosis and promotes NHEJ repair during DNA damage by mediating interaction with the Ku70–Ku80–DNA-PKcs complex.

    Evidence SILAC mass spectrometry, in vitro kinase assay, S135A mutagenesis, SAC assay, and Co-IP with NHEJ factors.

    PMID:35085551

    Open questions at the time
    • How the same phosphorylation directs BUB3 to different complexes in different cell-cycle contexts is unclear
    • Whether S135 phosphorylation affects BUB3 phospho-MELT reading not tested
  17. 2023 Medium

    Localization of BuGZ/BUB3 to SETD1A-bound promoter-TSS regions in leukemia linked BUB3 to chromatin-level transcriptional regulation, expanding its functional repertoire beyond kinetochore and telomere biology.

    Evidence Co-immunoprecipitation via FLOS domain screen, ChIP-seq, and functional proliferation assays in leukemia cells.

    PMID:37535603

    Open questions at the time
    • Whether BUB3 directly contacts chromatin at promoters or acts solely through BuGZ unclear
    • Transcriptional targets dependent on BUB3 at promoters not defined
    • Whether this chromatin role is conserved outside leukemia not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how BUB3 discriminates between mitotic, telomeric, chromatin, and cytoplasmic pools through context-dependent partner selection; the structural basis of methyl-lysine reading; whether BUB3 phospho-reading extends to additional substrates; and how ATM-Ser135 phosphorylation toggles BUB3 between SAC and DNA repair complexes.
  • No structural model of full BUB3–BubR1–CDC20 MCC at atomic resolution
  • Methyl-lysine reader mechanism of WD40 domain not structurally characterized
  • Context-dependent pool partitioning mechanism unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 2 GO:0042393 histone binding 1
Localization
GO:0005694 chromosome 7 GO:0005634 nucleus 3 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 10 R-HSA-69306 DNA Replication 1 R-HSA-73894 DNA Repair 1 R-HSA-74160 Gene expression (Transcription) 1
Partners
BUB1BUB1BCDC20KNL1RBBP7TRF2USP7ZNF207
Complex memberships
BUB3–BUB1BUB3–BuGZ/ZNF207MCC (BUB3–BubR1–CDC20)

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Human BUB3 localizes to kinetochores before chromosome alignment and interacts with BUB1 in mammalian cells. Deletion mapping showed the same domain of BUB1 required for BUB3 binding is required for BUB1 kinetochore localization, suggesting BUB3 recruits BUB1 to kinetochores to activate the spindle checkpoint. hBubR1 also binds BUB3 and localizes to kinetochores only when BUB3 is overexpressed. Co-immunoprecipitation, deletion mapping, immunofluorescence localization The Journal of cell biology High 9660858
1999 Murine BUB3 binds BUB1 to form a complex with protein kinase activity when expressed in insect cells. BUB3 localizes to kinetochores during prophase/prometaphase and is retained at high levels on lagging chromosomes but not correctly aligned chromosomes, consistent with a role in sensing microtubule attachment. Recombinant protein co-expression in insect cells, in vitro kinase assay, immunofluorescence Proceedings of the National Academy of Sciences of the United States of America High 10411903
2000 Bub3 gene disruption in mice causes embryonic lethality by day 6.5–7.5 post-coitus. Null embryos accumulate mitotic errors (micronuclei, chromatin bridging, lagging chromosomes) and fail to arrest in metaphase upon treatment with spindle-depolymerizing agents, establishing BUB3 as an essential spindle checkpoint component during early embryogenesis. Gene knockout in mice, mitotic index analysis, spindle poison challenge Genes & development High 10995385
2001 BUB1 is required for kinetochore localization of BUB3, MAD1, MAD2, and CENP-E in Xenopus egg extracts; reintroduction of either wild-type or kinase-dead BUB1 restores checkpoint and kinetochore localization of these proteins, indicating BUB1's kinase activity is dispensable for this scaffolding function. Immunodepletion and reconstitution in Xenopus egg extracts, immunofluorescence The Journal of cell biology High 11402067
2001 BUB3 interacts with MAD2, MAD3, and CDC20 through its WD40 repeats. Point mutations in the conserved WD40 motifs disrupt interactions with MAD2, MAD3, and CDC20 and abolish checkpoint response. BUB3 association with CDC20 is upregulated upon checkpoint activation and requires all kinetochore checkpoint proteins but not intact kinetochores, suggesting BUB3 serves as an interaction platform for checkpoint complex assembly. Co-immunoprecipitation, co-fractionation, WD40 point mutagenesis, checkpoint assays in yeast The EMBO journal High 11726501
2002 PARP-1 interacts with BUB3 (as well as CENPA and CENPB) at mammalian centromeres, and BUB3 undergoes poly(ADP-ribosyl)ation following DNA damage induction. Co-immunoprecipitation, Western blot, immunofluorescence The Journal of biological chemistry Medium 12011073
2002 PARP-2 interacts with BUB3 (as well as CENPA and CENPB) at active centromeres, demonstrated by co-immunoprecipitation, similarly to PARP-1. Co-immunoprecipitation, immunofluorescence on centromeres Human molecular genetics Low 12217960
2003 Haploinsufficiency of either RAE1 or BUB3 in mice causes mitotic checkpoint defects and chromosome missegregation. RAE1 overexpression can rescue both RAE1 and BUB3 haploinsufficiency, demonstrating overlapping and cooperating roles of these WD40 proteins in the mitotic checkpoint. Knockout mouse genetics, mitotic index, chromosome segregation analysis, epistasis/overexpression rescue The Journal of cell biology High 12551952
2003 Xenopus BUB3 (XBub3) is required for both activation and maintenance of spindle checkpoint arrest in egg extracts and is complexed with XBub1 and XBubR1 kinases. Two forms of XBub3 exist in egg extracts; only one form is present in XTC cells, where it localizes diffusely in the nucleus during interphase and recruits to kinetochores during early prophase. Immunodepletion of Xenopus egg extracts, co-immunoprecipitation, immunofluorescence Journal of cell science High 12538762
2004 Crystal structure of S. cerevisiae BUB3 at 2.35 Å resolution reveals a seven-bladed β-propeller with conserved surfaces on the top face and lateral surface (blades 5–6) proposed as interaction sites for GLEBS motifs in BUB1 and MAD3/BubR1. X-ray crystallography at 2.35 Å resolution Journal of molecular biology High 15544799
2007 Crystal structures of yeast BUB3 bound to GLEBS-motif peptides from MAD3 and BUB1 show the peptides snake along the top surface of the β-propeller. The interactions are similar for both partners and mutually exclusive. Calorimetry gives Kd ~5 μM for GLEBS peptide binding. Mutations disrupting the interface cause checkpoint deficiency and chromosome instability. X-ray crystallography, isothermal titration calorimetry, negative-stain EM, mutagenesis, checkpoint and chromosome stability assays Proceedings of the National Academy of Sciences of the United States of America High 17227844
2007 The dynein light chain DYNLT3 directly binds BUB3 exclusively (not other dynein light chains), linking cytoplasmic dynein to the spindle checkpoint complex at kinetochores. DYNLT3 is present at kinetochores during prometaphase and is depleted upon chromosome alignment, paralleling BUB3 behavior. Knockdown of DYNLT3 increases mitotic index. GST pull-down, co-immunoprecipitation, immunofluorescence, siRNA knockdown The Journal of biological chemistry Medium 17289665
2008 BUB3 RNAi in human cells causes defective kinetochore-microtubule attachments with misaligned chromosomes predominantly in side-on configuration, indicating BUB3 is required for establishing stable end-on bipolar attachments. After Aurora B inhibition, alignment defects become worse in BUB3-depleted cells, placing BUB3 in a pathway distinct from BubR1 for kinetochore-microtubule regulation. RNAi knockdown, high-resolution microscopy, kinetochore-microtubule attachment analysis, Aurora B inhibition epistasis Molecular biology of the cell High 18199686
2009 BUB3 freed from BUB1 associates with p73 (specifically on Y99-phosphorylated p73) to activate caspase-independent mitotic death (CIMD). This interaction occurs specifically in cells undergoing CIMD triggered by partial BUB1 depletion and kinetochore-microtubule attachment defects. Co-immunoprecipitation, RNAi, cell death assays Cell death and differentiation Medium 20057499
2012 MPS1/MPH1 kinase phosphorylates conserved MELT motifs in the kinetochore scaffold SPC7/KNL1, and this phosphorylation is required for recruitment of BUB1 and BUB3 to kinetochores to maintain the spindle assembly checkpoint signal. Genetic and biochemical epistasis in fission yeast, phospho-mutant analysis, kinetochore recruitment assays Current biology : CB High 22521786
2013 BUB3 is the phospho-MELT (MELpT) reader: its β-propeller contains an exceptionally conserved interface that directly docks the phosphorylated MELT sequence in a novel binding mode. Mutations targeting this interface prevent kinetochore recruitment of BUB1 and cause a checkpoint defect, establishing BUB3 as the phospho-amino acid adaptor that reads Mps1-phosphorylated KNL1/Spc105 to recruit SAC components. Crystal structure of BUB3–MELpT complex, mutagenesis, kinetochore recruitment assay in cells, checkpoint functional assay eLife High 24066227
2014 BUB3 promotes mitotic checkpoint signaling by two mechanisms: (1) facilitating BubR1 binding to unattached kinetochores and enhancing CDC20 recruitment by BubR1's internal CDC20 binding site; (2) downstream of kinetochores, stimulating BubR1's N-terminal CDC20 binding domain to engage a site on CDC20 exposed by initial MAD2 binding, generating the final BUB3–BubR1–CDC20 MCC that selectively inhibits APC/C. In vitro reconstitution, cell-based complementation assays, APC/C ubiquitination assay Proceedings of the National Academy of Sciences of the United States of America High 25246557
2014 BuGZ/ZNF207 directly binds and stabilizes BUB3 via its conserved GLEBS domain. BuGZ also uses its microtubule-binding domain to enhance loading of BUB3 onto kinetochores during prometaphase in a microtubule-dependent manner, promoting chromosome alignment. Loss of BuGZ reduces BUB3 and BUB1 at kinetochores. Identification by Spemix screen, in vitro binding, RNAi, live-cell imaging, kinetochore loading assays (two independent studies) Developmental cell High 24462186 24462187
2015 Human KNL1 MELT-containing repeats are regulated sequentially: MPS1 phosphorylates MELT motifs first, enabling subsequent phosphorylation of a vertebrate-specific SHT motif C-terminal to MELT. Phospho-SHT (SHpT) synergizes with MELpT in BUB3/BUB1 binding in vitro and in cells. BUB3 mutated in the predicted SHpT-binding surface cannot localize to kinetochores. Systematic mutational screening of KNL1 repeats, in vitro binding assays, BUB3 interface mutagenesis, kinetochore localization in cells Molecular cell High 25661489
2015 BUB3 promotes Cdc20-dependent APC/C activation in budding yeast independently of the spindle checkpoint: bub3Δ cells have impaired APC/C–CDC20 binding and a metaphase delay rescued by CDC20 overexpression. Kinetochore localization of BUB3 (but not BUB1) is required for this function. Genetic deletion analysis in S. cerevisiae, Co-IP of APC/C–CDC20, CDC20 overexpression rescue, co-localization microscopy The Journal of cell biology Medium 25987604
2015 BUB3–BubR1 complex at DNA breaks facilitates proper segregation of broken chromosomes by sequestering CDC20 in a BubR1 KEN box-dependent manner, causing local APC/C inhibition around broken chromosome fragments. APC/C activity biosensor, RNAi, immunofluorescence in Drosophila The Journal of cell biology Medium 26553926
2016 Multisite binding of BUB3 to the SPC7 MELT array toggles the spindle checkpoint switch by permitting MPS1-dependent interaction of BUB1 with the MAD1–MAD2 complex in fission yeast. Genetic analysis, phospho-mutant studies, co-immunoprecipitation of BUB1–MAD1–MAD2 Current biology : CB Medium 27618268
2016 The GLEBS motif of BubR1 mediates a high-affinity, enthalpy-driven, 1:1 interaction with BUB3. Small regions in the N and C termini of the GLEBS domain create 'hotspots' that modulate affinity, kinetics, and thermodynamics. Disruption of endogenous BubR1·BUB3 complexes in cancer cells abrogates SAC and induces apoptosis. Surface plasmon resonance, ITC, siRNA knockdown, structural mapping The Journal of biological chemistry High 27030009
2017 The BubR1 loop region directs BUB3 to phosphorylated targets distinct from those recognized via the BUB1 loop. BubR1 loop mutants bind BUB3 and form MCC normally in vitro but have reduced ability to inhibit APC/C, indicating BUB3–BubR1 recognition of phosphorylated APC/C targets is required for full APC/C inhibition. In vitro MCC reconstitution, APC/C inhibition assay, mutagenesis Current biology : CB High 28943088
2018 The BUB3–BUB1 complex binds telomeres during S phase and promotes telomere DNA replication. Loss of BUB3–BUB1 causes fragile and shortened telomeres. TRF2 targets BUB1–BUB3 to telomeres, and BUB1 directly phosphorylates TRF1 to promote recruitment of BLM helicase for resolving replication stress. BUB3's telomere-binding ability and BUB1's kinase activity are both required. ChIP, co-immunoprecipitation, in vitro kinase assay, telomere FISH, RNAi/knockout Molecular cell High 29727616
2020 CRL4 ubiquitin ligase complex ubiquitinates BUB3 during mitosis via its adaptor RBBP7, targeting BUB3 for degradation to terminate the spindle assembly checkpoint and enable mitotic exit. During interphase, BUB3 is protected from CRL4-mediated degradation by associating with PML nuclear bodies. Co-immunoprecipitation, ubiquitination assay, RNAi, cell fractionation, mitotic exit timing Nature communications High 31911655
2021 EZH2 methylates FOXA1 at lysine-295, and this methylation is recognized by BUB3's WD40 domain, which then recruits the deubiquitinase USP7 to remove ubiquitin from FOXA1, enhancing its protein stability in prostate cancer. Co-immunoprecipitation, in vitro methylation assay, ubiquitination assay, mutagenesis Science advances High 33827814
2021 The long noncoding RNA CRYBG3 directly binds BUB3 protein (via residues 261–317 of CRYBG3) and disrupts its interaction with CDC20, leading to MCC dysfunction, aneuploidy, and tumorigenesis. RNA immunoprecipitation, Co-IP, overexpression/knockdown functional assays Oncogene Medium 33564066
2022 ATM kinase phosphorylates BUB3 at serine-135 both in vitro and in vivo during mitosis, promoting SAC activation by enhancing BUB1 activation. During DNA damage, the same phosphorylation promotes interaction with the Ku70–Ku80–DNA-PKcs complex to facilitate non-homologous end-joining repair, revealing dual context-dependent roles of this modification. SILAC mass spectrometry, in vitro kinase assay, mutagenesis (S135A), SAC assay, Co-IP with NHEJ complex The Journal of biological chemistry High 35085551
2022 MST1/2 kinases form a disease-specific interaction with BUB3 in PAH pulmonary arterial vascular smooth muscle cells, supporting ECM- and USP10-dependent BUB3 accumulation, upregulation of Akt-mTORC1, and cell proliferation/survival. Unbiased proteomics, Co-IP, gain/loss-of-function, pharmacological inhibition Circulation research Medium 35124974
2014 USP7 deubiquitinase interacts with and stabilizes BUB3; USP7 depletion reduces BUB3 levels and causes mitotic abnormalities including lagging chromosomes, demonstrating USP7 as a positive regulator of BUB3 protein stability. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, small molecule inhibition Oncotarget Medium 25003721
2009 TAp73α (but not p53 or other p73 isoforms) directly binds BUB1 and BUB3 via co-immunoprecipitation, and TAp73α overexpression induces polyploidy, suggesting interference with the mitotic checkpoint via BUB protein interaction. Co-immunoprecipitation, overexpression, ploidy analysis Cell cycle (Georgetown, Tex.) Low 19182530
2018 Mitotic arrest induces p38-dependent phosphorylation of BUB3 at Ser211, which promotes interaction between BUB3 and DMAP1. The DMAP1/BUB3 complex is recruited by TAp73 to the BCL2L1 promoter, mediating DNA methylation and repression of this anti-apoptotic gene to promote cell death. c-Src phosphorylates DMAP1 at Tyr246 in pancreatic cancer, impairing DMAP1/BUB3 interaction and conferring resistance to mitotic stress. Co-immunoprecipitation, phospho-mutant analysis, ChIP, DNA methylation assay, kinase assay Molecular cancer Medium 30553276
2015 A motif from Lys216 to Lys222 in human BUB3 is required for nuclear localization and kinetochore targeting. A deletion or charge-reversal mutant in this region impairs kinetochore localization and mitotic checkpoint arrest. The mutant retains ability to bind BUB1, MAD2, and BubR1 but shows impaired association with CENP-A and KNL1, indicating the nuclear localization signal is also critical for centromeric anchoring. Mutagenesis, localization assays, co-immunoprecipitation, checkpoint arrest assay The Journal of biological chemistry Medium 25814666
2020 In budding yeast meiosis, BUB3 is crucial for correction of chromosome attachment errors and for Aurora B/Ipl1 kinetochore localization. Depletion of BUB3 causes premature PP1 localization to kinetochores, antagonizing Ipl1-mediated phosphorylation and causing massive chromosome missegregation. This reveals a role for the BUB1–BUB3 pathway in balancing Ipl1 and PP1 activity at kinetochores during meiosis. Genetic deletion, kinetochore protein localization by microscopy, chromosome segregation analysis in meiosis The Journal of cell biology Medium 32328625
2020 WAPL interacts with BUB3 (identified by immunoprecipitation and mass spectrometry) and maintains BUB3 protein levels in mouse oocytes. Depletion of WAPL reduces BUB3 protein, inactivates the spindle assembly checkpoint, and causes aneuploidy; exogenous BUB3 rescues meiotic defects in WAPL-depleted oocytes. Co-immunoprecipitation, mass spectrometry, RNAi, overexpression rescue, immunofluorescence Science advances Medium 32284991
2023 The H3K4 methyltransferase SETD1A FLOS domain binds BuGZ/BUB3 in leukemia cells. BuGZ/BUB3 localize to SETD1A-bound promoter-TSS regions. The GLEBS motif and intrinsically disordered region of BuGZ are required for SETD1A binding and leukemia cell proliferation, linking BUB3 to transcriptional regulation in leukemia. Co-immunoprecipitation/FLOS domain screen, ChIP-seq, functional inhibition assays EMBO reports Medium 37535603

Source papers

Stage 0 corpus · 81 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
2003 Rae1 is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation. The Journal of cell biology 302 12551952
2012 Phosphodependent recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 kinase maintains the spindle checkpoint. Current biology : CB 241 22521786
2000 Bub3 gene disruption in mice reveals essential mitotic spindle checkpoint function during early embryogenesis. Genes & development 213 10995385
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
2013 Bub3 reads phosphorylated MELT repeats to promote spindle assembly checkpoint signaling. eLife 189 24066227
2001 Bub3 interaction with Mad2, Mad3 and Cdc20 is mediated by WD40 repeats and does not require intact kinetochores. The EMBO journal 159 11726501
2006 Early aging-associated phenotypes in Bub3/Rae1 haploinsufficient mice. The Journal of cell biology 148 16476774
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
2009 Bub3 is a spindle assembly checkpoint protein regulating chromosome segregation during mouse oocyte meiosis. PloS one 105 19888327
2002 Centromere proteins Cenpa, Cenpb, and Bub3 interact with poly(ADP-ribose) polymerase-1 protein and are poly(ADP-ribosyl)ated. The Journal of biological chemistry 100 12011073
2015 Sequential multisite phospho-regulation of KNL1-BUB3 interfaces at mitotic kinetochores. Molecular cell 94 25661489
2007 Structural analysis of Bub3 interactions in the mitotic spindle checkpoint. Proceedings of the National Academy of Sciences of the United States of America 87 17227844
1999 Retention of the BUB3 checkpoint protein on lagging chromosomes. Proceedings of the National Academy of Sciences of the United States of America 84 10411903
2014 A microtubule-associated zinc finger protein, BuGZ, regulates mitotic chromosome alignment by ensuring Bub3 stability and kinetochore targeting. Developmental cell 80 24462186
1998 Localization of the Drosophila checkpoint control protein Bub3 to the kinetochore requires Bub1 but not Zw10 or Rod. Chromosoma 80 9914369
2002 Poly(ADP-ribose) polymerase 2 localizes to mammalian active centromeres and interacts with PARP-1, Cenpa, Cenpb and Bub3, but not Cenpc. Human molecular genetics 79 12217960
2008 The human spindle assembly checkpoint protein Bub3 is required for the establishment of efficient kinetochore-microtubule attachments. Molecular biology of the cell 77 18199686
2013 Germline mutations in the spindle assembly checkpoint genes BUB1 and BUB3 are risk factors for colorectal cancer. Gastroenterology 72 23747338
2008 Kinetochore-microtubule interactions "in check" by Bub1, Bub3 and BubR1: The dual task of attaching and signalling. Cell cycle (Georgetown, Tex.) 69 18594200
2014 BuGZ is required for Bub3 stability, Bub1 kinetochore function, and chromosome alignment. Developmental cell 68 24462187
2005 Increased chromosome instability but not cancer predisposition in haploinsufficient Bub3 mice. Genes, chromosomes & cancer 64 15898111
2021 Posttranslational regulation of FOXA1 by Polycomb and BUB3/USP7 deubiquitin complex in prostate cancer. Science advances 61 33827814
2018 The BUB3-BUB1 Complex Promotes Telomere DNA Replication. Molecular cell 55 29727616
2013 A tumor suppressor role of the Bub3 spindle checkpoint protein after apoptosis inhibition. The Journal of cell biology 51 23609535
2001 Molecular analysis of the mitotic checkpoint genes BUB1, BUBR1 and BUB3 in human lung cancers. Cancer letters 51 11146226
2004 Disruption of astral microtubule contact with the cell cortex activates a Bub1, Bub3, and Mad3-dependent checkpoint in fission yeast. Molecular biology of the cell 45 15146064
2022 Noncanonical HIPPO/MST Signaling via BUB3 and FOXO Drives Pulmonary Vascular Cell Growth and Survival. Circulation research 44 35124974
2007 The DYNLT3 light chain directly links cytoplasmic dynein to a spindle checkpoint protein, Bub3. The Journal of biological chemistry 40 17289665
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2016 Bub3-Bub1 Binding to Spc7/KNL1 Toggles the Spindle Checkpoint Switch by Licensing the Interaction of Bub1 with Mad1-Mad2. Current biology : CB 38 27618268
2005 The Drosophila Bub3 protein is required for the mitotic checkpoint and for normal accumulation of cyclins during G2 and early stages of mitosis. Journal of cell science 38 15615783
2009 Bub1 and Bub3 promote the conversion from monopolar to bipolar chromosome attachment independently of shugoshin. EMBO reports 36 19680287
2004 Crystal structure of the spindle assembly checkpoint protein Bub3. Journal of molecular biology 34 15544799
2014 Bimodal activation of BubR1 by Bub3 sustains mitotic checkpoint signaling. Proceedings of the National Academy of Sciences of the United States of America 33 25246557
2020 The RepID-CRL4 ubiquitin ligase complex regulates metaphase to anaphase transition via BUB3 degradation. Nature communications 31 31911655
2018 Role of the BUB3 protein in phragmoplast microtubule reorganization during cytokinesis. Nature plants 28 29967519
2009 TAp73alpha binds the kinetochore proteins Bub1 and Bub3 resulting in polyploidy. Cell cycle (Georgetown, Tex.) 27 19182530
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2010 BUB3 that dissociates from BUB1 activates caspase-independent mitotic death (CIMD). Cell death and differentiation 24 20057499
2005 Allelic loss at 10q26 in osteosarcoma in the region of the BUB3 and FGFR2 genes. Cancer genetics and cytogenetics 23 15796961
2018 Oral lichen planus and malignant transformation: The role of p16, Ki-67, Bub-3 and SOX4 in assessing precancerous potential. Experimental and therapeutic medicine 22 29731815
2015 Bub3 promotes Cdc20-dependent activation of the APC/C in S. cerevisiae. The Journal of cell biology 22 25987604
2008 Genetic analysis of the spindle checkpoint genes san-1, mdf-2, bub-3 and the CENP-F homologues hcp-1 and hcp-2 in Caenorhabditis elegans. Cell division 22 18248670
2008 The Arabidopsis checkpoint protein Bub3.1 is essential for gametophyte development. Frontiers in bioscience : a journal and virtual library 22 18508582
2002 Molecular cloning and characterization of the human budding uninhibited by benomyl (BUB3) promoter. Gene 22 12242018
2008 Schizosaccharomyces pombe Bub3 is dispensable for mitotic arrest following perturbed spindle formation. Genetics 21 18505884
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2003 Analysis of Bub3 spindle checkpoint function in Xenopus egg extracts. Journal of cell science 18 12538762
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2018 Spindlin1 alters the metaphase to anaphase transition in meiosis I through regulation of BUB3 expression in porcine oocytes. Journal of cellular physiology 16 30317618
2014 Mad2, Bub3, and Mps1 regulate chromosome segregation and mitotic synchrony in Giardia intestinalis, a binucleate protist lacking an anaphase-promoting complex. Molecular biology of the cell 15 25057014
2024 YY2/BUB3 Axis promotes SAC Hyperactivation and Inhibits Colorectal Cancer Progression via Regulating Chromosomal Instability. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 14 38682484
2022 Dual-functional significance of ATM-mediated phosphorylation of spindle assembly checkpoint component Bub3 in mitosis and the DNA damage response. The Journal of biological chemistry 12 35085551
2018 C-Src confers resistance to mitotic stress through inhibition DMAP1/Bub3 complex formation in pancreatic cancer. Molecular cancer 11 30553276
2016 Functional and Structural Characterization of Bub3·BubR1 Interactions Required for Spindle Assembly Checkpoint Signaling in Human Cells. The Journal of biological chemistry 11 27030009
2024 The Arabidopsis BUB1/MAD3 family protein BMF3 requires BUB3.3 to recruit CDC20 to kinetochores in spindle assembly checkpoint signaling. Proceedings of the National Academy of Sciences of the United States of America 10 38466841
2024 Kinetoplastid kinetochore proteins KKT14-KKT15 are divergent Bub1/BubR1-Bub3 proteins. Open biology 9 38862021
2023 SETD1A function in leukemia is mediated through interaction with mitotic regulators BuGZ/BUB3. EMBO reports 8 37535603
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2021 Yeast Fin1-PP1 dephosphorylates an Ipl1 substrate, Ndc80, to remove Bub1-Bub3 checkpoint proteins from the kinetochore during anaphase. PLoS genetics 6 34033659
2017 Caenorhabditis elegans BUB-3 and SAN-1/MAD3 Spindle Assembly Checkpoint Components Are Required for Genome Stability in Response to Treatment with Ionizing Radiation. G3 (Bethesda, Md.) 6 29046436
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2025 mir-188-5p emerges as an oncomir to promote chronic myeloid leukemia via upregulation of BUB3 and SUMO2. Molecular biology reports 1 40019654
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2023 Analysis of Bub3 and Nup75 in the Drosophila male germline lineage. Cells & development 0 37286104
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