Affinage

BUB3

Mitotic checkpoint protein BUB3 · UniProt O43684

Length
328 aa
Mass
37.2 kDa
Annotated
2026-06-09
79 papers in source corpus 41 papers cited in narrative 40 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

BUB3 is a seven-bladed WD40 β-propeller protein that functions as the central scaffold of the spindle assembly checkpoint (SAC), coupling kinetochore phospho-signals to inhibition of the anaphase-promoting complex (PMID:15544799, PMID:24066227, PMID:10995385). At unattached kinetochores, BUB3 reads MELT motifs of the KNL1/Spc105 scaffold that are phosphorylated by the MPS1 kinase: an exceptionally conserved interface on the side of its propeller docks phospho-MELT, and in vertebrates a C-terminal SHT motif is phosphorylated only after prior MELT phosphorylation, providing sequential multisite control of the KNL1-BUB3 interface (PMID:22521786, PMID:24066227, PMID:25661489). Through this localization BUB3 recruits the SAC kinases BUB1 and BubR1, binding their GLEBS motifs along the top surface of the propeller in a mutually exclusive, high-affinity manner, and is itself required for kinetochore loading of BUB1 (PMID:9660858, PMID:17227844, PMID:27030009). Beyond kinetochore docking, BUB3 promotes assembly of the mitotic checkpoint complex by facilitating two distinct BubR1-Cdc20 interactions that generate the final BUB3-BubR1-Cdc20 inhibitor of APC/C-Cdc20, preventing premature anaphase (PMID:25246557, PMID:28943088). Genetic loss of Bub3 in mice and other organisms causes chromosome missegregation, checkpoint failure, and embryonic lethality, and BUB3 cooperates with Rae1 in the mitotic checkpoint (PMID:10995385, PMID:12551952). BUB3 abundance is set by opposing activities—the deubiquitinase USP7 and the chaperone BuGZ/ZNF207 stabilize it, while the RepID/RBBP7-CRL4 ubiquitin ligase ubiquitinates BUB3 to terminate the checkpoint at mitotic exit (PMID:24462186, PMID:24462187, PMID:31911655, PMID:25003721). The protein additionally functions in kinetochore-microtubule attachment correction by balancing Aurora B/Ipl1 and PP1 activity (PMID:18199686, PMID:32328625), in telomere replication as part of a TRF2-recruited BUB3-BUB1 complex (PMID:29727616), and in the DNA damage response through ATM-mediated phosphorylation of Ser135 that connects it to NHEJ machinery (PMID:35085551). In a non-mitotic context, BUB3 reads EZH2-methylated FOXA1 and recruits USP7 to stabilize FOXA1 in prostate cancer cells, repurposing its WD40 reader function (PMID:33827814).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1998 High

    Establishing that BUB3 is a kinetochore-localized binding partner of BUB1 defined its position at the apex of the checkpoint recruitment hierarchy.

    Evidence Co-IP, deletion mapping and overexpression/localization in mammalian cells

    PMID:9660858

    Open questions at the time
    • Did not define the structural basis of the BUB1-BUB3 interaction
    • Direction of recruitment between BUB1 and BUB3 not fully resolved
  2. 2000 High

    Genetic knockout proved BUB3 is an essential, non-redundant component of the spindle checkpoint in vivo rather than a dispensable accessory factor.

    Evidence Bub3-null mouse embryos with spindle-depolymerizing drug challenge

    PMID:10995385

    Open questions at the time
    • Embryonic lethality precluded analysis of adult/tissue-specific roles
    • Did not separate checkpoint from attachment functions
  3. 2001 High

    BUB1 was shown to recruit BUB3 to kinetochores through a structural, kinase-independent role, and BUB3 was placed in a WD40-dependent platform for MCC-like interactions with Cdc20/Mad2/Mad3.

    Evidence Xenopus immunodepletion/add-back with kinase-dead BUB1; yeast two-hybrid and WD40 point-mutant checkpoint assays

    PMID:11402067 PMID:11726501

    Open questions at the time
    • Atomic basis of WD40-mediated partner binding not yet defined
    • How kinetochore docking is achieved remained unknown
  4. 2004 High

    The crystal structure revealed BUB3 as a seven-bladed β-propeller and predicted the GLEBS-binding surfaces, providing a structural framework for its scaffold function.

    Evidence X-ray crystallography of S. cerevisiae Bub3p at 2.35 Å

    PMID:15544799

    Open questions at the time
    • Predicted binding sites awaited validation with bound partner
    • No phospho-ligand complex
  5. 2007 High

    Co-crystal structures with GLEBS peptides showed BUB1 and BubR1 bind the same propeller surface in a mutually exclusive mode, explaining how BUB3 selects between the two checkpoint kinases.

    Evidence X-ray crystallography, ITC (Kd ~5 µM), EM and interface-mutant checkpoint/CIN assays

    PMID:17227844

    Open questions at the time
    • Did not address phospho-MELT recognition
    • Functional consequence of mutual exclusivity in cells not fully mapped
  6. 2012 High

    Identifying MPS1-phosphorylated MELT motifs of KNL1/Spc7 as the kinetochore recruitment signal explained how BUB3-BUB1 is loaded in a phospho-regulated manner.

    Evidence Phospho-specific and MELT-mutant checkpoint analysis in fission yeast

    PMID:22521786

    Open questions at the time
    • Did not identify which subunit directly reads phospho-MELT
    • Vertebrate-specific elements not addressed
  7. 2013 High

    BUB3 itself was identified as the direct reader of phospho-MELT, with a conserved propeller-side interface, unifying its docking and scaffold roles.

    Evidence Structure-guided mutagenesis with kinetochore recruitment and checkpoint assays

    PMID:24066227

    Open questions at the time
    • Stoichiometry of multisite MELT engagement not fully defined
    • Vertebrate SHT contribution not yet known
  8. 2014 High

    BUB3 abundance and kinetochore loading were shown to be actively controlled by BuGZ and USP7, defining post-translational regulation of checkpoint capacity.

    Evidence Direct binding assays, RNAi/rescue with BuGZ GLEBS mutants, USP7 depletion and Western blot

    PMID:24462186 PMID:24462187 PMID:25003721

    Open questions at the time
    • USP7 evidence rests on Co-IP plus depletion phenotype
    • Precise ubiquitination sites not defined here
  9. 2014 High

    Reconstitution showed BUB3 drives MCC formation through two distinct BubR1-Cdc20 interactions, mechanistically linking kinetochore signaling to APC/C inhibition.

    Evidence In vitro MCC reconstitution with cell-based checkpoint assays and fractionation

    PMID:25246557

    Open questions at the time
    • Quantitative kinetics of the two-step Cdc20 engagement not resolved
    • In vivo ordering of events partially inferred
  10. 2015 High

    A vertebrate SHT motif and sequential MELT-then-SHT phosphorylation were shown to synergize for BUB3 binding, revealing layered phospho-control of the KNL1-BUB3 interface.

    Evidence Systematic mutational screening, in vitro binding and BUB3 mutagenesis in cells

    PMID:25661489

    Open questions at the time
    • Number of active repeats sufficient for signaling not fully defined
    • Kinetics of MPS1 priming not resolved
  11. 2016 High

    Biophysical and biophysically-anchored functional work established the BUB3-BubR1 GLEBS interaction as a slow-dissociating 1:1 complex whose disruption phenocopies BUB3 loss, and showed multisite MELT binding toggles the checkpoint switch.

    Evidence SPR/ITC with knockdown and peptide competition; fission yeast epistasis and Co-IP

    PMID:27030009 PMID:27618268

    Open questions at the time
    • GLEBS-flanking 'hotspot' contributions in vivo not fully mapped
    • Switch-like behavior quantification incomplete
  12. 2017 High

    The BubR1 loop region was shown to direct BUB3 to phospho-targets required for APC/C inhibition, distinguishing the BubR1 and BUB1 arms of BUB3 function.

    Evidence In vitro MCC reconstitution and APC/C inhibition with loop mutants in cells

    PMID:28943088

    Open questions at the time
    • Identity of the relevant phospho-targets not fully defined
    • Kinase responsible not pinned down here
  13. 2018 High

    BUB3 was shown to function outside the checkpoint in telomere replication as part of a TRF2-recruited BUB3-BUB1 complex.

    Evidence ChIP, telomere FISH, kinase assays and domain/kinase-dead mutants

    PMID:29727616

    Open questions at the time
    • Whether BUB3 reads a phospho-mark at telomeres unknown
    • Direct BUB3 DNA/chromatin contacts not defined
  14. 2018 Medium

    Stress-activated kinases were shown to phosphorylate BUB3 (Ser211) to redirect it into a DMAP1-dependent transcriptional/apoptotic program, expanding BUB3 beyond mitosis.

    Evidence Co-IP, phospho-mutants, ChIP, reporter and tumor models

    PMID:30553276

    Open questions at the time
    • Single-lab mechanism in a specific cancer context
    • Generality of the DMAP1/BUB3 axis not established
  15. 2020 Medium

    CRL4-mediated ubiquitination of BUB3 was identified as the trigger for checkpoint termination, completing the activate/silence cycle of BUB3 regulation.

    Evidence Ubiquitination assays, Co-IP, fractionation and mitotic timing with RepID/RBBP7 components

    PMID:31911655

    Open questions at the time
    • BUB3 ubiquitination sites not mapped
    • PML-body protection mechanism rests on single study
  16. 2020 Medium

    BUB3 was shown to balance Aurora B/Ipl1 and PP1 at kinetochores to correct attachment errors, separating this activity from pure checkpoint signaling.

    Evidence Conditional Bub3 depletion in yeast meiosis with kinase/phosphatase localization readouts; Wapl-BUB3 level control in oocytes

    PMID:32284991 PMID:32328625

    Open questions at the time
    • Direct molecular link between BUB3 and Ipl1/PP1 recruitment unresolved
    • Conservation in human somatic mitosis not addressed
  17. 2021 Medium

    BUB3 was shown to function as a WD40 methyl-reader of EZH2-methylated FOXA1, recruiting USP7 to stabilize FOXA1, demonstrating a non-mitotic reader activity.

    Evidence Methylation/ubiquitination assays, domain mutants and prostate cancer growth assays

    PMID:33827814

    Open questions at the time
    • Whether methyl- and phospho-reading use overlapping surfaces unknown
    • Single cancer-context demonstration
  18. 2022 High

    ATM phosphorylation of BUB3 Ser135 was shown to link it to both SAC activation and NHEJ, integrating BUB3 into the DNA damage response.

    Evidence SILAC-MS, in vitro kinase assay, Ser135 mutagenesis with checkpoint and DNA repair readouts

    PMID:35085551

    Open questions at the time
    • How Ser135 phosphorylation alters BUB3 partner choice unclear
    • Structural impact of the modification undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BUB3 partitions its single WD40 surface among phospho-MELT/SHT, GLEBS motifs, and methylated FOXA1, and how post-translational marks (Ser135, Ser211, ubiquitin) switch it between these mutually distinct functional programs, remains unresolved.
  • No structural model integrating phospho-reading, GLEBS binding, and methyl-reading on one propeller
  • Mechanism by which modifications redirect BUB3 between mitotic and non-mitotic complexes unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0140299 molecular sensor activity 2 GO:0042393 histone binding 1
Localization
GO:0005694 chromosome 3 GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-73894 DNA Repair 2 R-HSA-69306 DNA Replication 1
Partners
BUB1BUBR1CDC20KNL1RAE1TRF2USP7ZNF207
Complex memberships
BUB1-BUB3 complexBubR1-BUB3 complexmitotic checkpoint complex (MCC)

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Human BUB3 (hBub3) localizes to kinetochores before chromosome alignment and physically interacts with BUB1 in mammalian cells. Deletion mapping identified the domain of BUB1 required for BUB3 binding, and this same domain is required for kinetochore localization of BUB1, establishing that BUB3 recruits BUB1 to the kinetochore. hBubR1 also binds BUB3 in mammalian cells and localizes to kinetochores during prometaphase when BUB3 is overexpressed. Co-immunoprecipitation, deletion mapping, overexpression/localization studies in mammalian cells The Journal of cell biology High 9660858
1999 Murine Bub3 (mBub3) binds Bub1 to form a complex with protein kinase activity when expressed in insect cells. Bub3 localizes to kinetochores during prophase/prometaphase, and high levels remain on lagging chromosomes but not correctly aligned chromosomes, consistent with a role in sensing microtubule attachment. Recombinant protein expression in insect cells, co-immunoprecipitation, kinase assay, immunofluorescence microscopy Proceedings of the National Academy of Sciences of the United States of America High 10411903
2000 Bub3 is essential for early embryonic development in mice; Bub3-null embryos accumulate mitotic errors (micronuclei, chromatin bridges, lagging chromosomes) from day 4.5 pc, and null embryos treated with a spindle-depolymerizing agent fail to arrest in metaphase, establishing Bub3 as a required component of the spindle checkpoint pathway. Bub3 gene disruption (knockout mice), spindle checkpoint assay with microtubule-depolymerizing drug Genes & development High 10995385
2001 Xenopus Bub1 is required for kinetochore localization of Bub3 (as well as Mad1, Mad2, and CENP-E); immunodepletion of Bub1 abolishes spindle checkpoint function and kinetochore binding of Bub3, and re-introduction of kinase-deficient Bub1 restores both, showing that the structural (non-kinase) role of Bub1 is sufficient to recruit Bub3 to kinetochores. Immunodepletion in Xenopus egg extracts, add-back of wild-type vs. kinase-deficient Bub1, immunofluorescence The Journal of cell biology High 11402067
2001 Yeast Bub3 interacts with Cdc20, Mad2, and Mad3 via its WD40 repeats. Point mutations in the conserved WD40 motifs of Bub3 disrupt association with Mad2, Mad3, and Cdc20 and abrogate checkpoint response. Bub3–Cdc20 complex formation requires all kinetochore checkpoint proteins but does not require intact kinetochores, suggesting Bub3 serves as a platform for MCC-like interactions. Yeast two-hybrid, co-fractionation, WD40 point-mutant analysis, checkpoint assay The EMBO journal High 11726501
2002 Bub3 interacts with PARP-1 and is poly(ADP-ribosyl)ated following induction of DNA damage, as demonstrated by immunoprecipitation and Western blot, linking Bub3 to the DNA damage response at centromeres. Co-immunoprecipitation, Western blot, immunofluorescence The Journal of biological chemistry Medium 12011073
2002 PARP-2 interacts with Bub3 at active centromeres as demonstrated by co-immunoprecipitation; PARP-2 localizes to centromeres in a cell-cycle-dependent manner, accumulating during prometaphase/metaphase. Co-immunoprecipitation, immunofluorescence on pseudodicentric chromosome and neocentromere Human molecular genetics Medium 12217960
2003 Haplo-insufficiency of either Rae1 or Bub3 in mice causes mitotic checkpoint defects and chromosome missegregation; overexpression of Rae1 rescues both Rae1 and Bub3 haplo-insufficiency, demonstrating overlapping and cooperating roles in the mitotic checkpoint. Rae1-null and Bub3-null mice are embryonic lethal. Compound Rae1/Bub3 haplo-insufficient mice show much greater rates of premature sister chromatid separation than single haplo-insufficient mice. Knockout/haploinsufficiency mouse genetics, mitotic checkpoint assay, rescue by Rae1 overexpression The Journal of cell biology High 12551952
2003 Xenopus Bub3 (XBub3) is required for both activation and maintenance of the spindle checkpoint in egg extracts; XBub3 exists in two forms in extracts, both complexed with XBub1 and XBubR1 kinases. During interphase, XBub3 is diffusely nuclear, then recruited to kinetochores in early prophase, departing after chromosome alignment. Antibody-mediated inhibition in Xenopus egg extracts, co-immunoprecipitation, immunofluorescence Journal of cell science Medium 12538762
2004 Crystal structure of Saccharomyces cerevisiae Bub3p determined at 2.35 Å resolution reveals a seven-bladed β-propeller with extended loops forming a cleft on the top face. Conserved residues on the top face and lateral surface (blades 5–6) are proposed as the binding sites for GLEBS motifs in Bub1 and Mad3/BubR1. X-ray crystallography Journal of molecular biology High 15544799
2005 Drosophila Bub3 is required to prevent premature sister chromatid separation and aneuploidy during normal mitosis, and loss of Bub3 causes a delay in mitotic entry attributed to failure to accumulate mitotic cyclins A and B due to inappropriate APC/C activity; mutations in APC/C subunit cdc27 partially rescue this phenotype, establishing Bub3 as a regulator of APC/C during G2 and early mitosis. Drosophila Bub3 mutation and RNAi depletion, genetic epistasis with cdc27 mutant, time-lapse analysis Journal of cell science High 15615783
2007 Crystal structures of Bub3 with GLEBS-motif peptides from Mad3 and Bub1 show the peptide snaking along the top surface of the β-propeller in a previously unknown binding mode. The Mad3 and Bub1 GLEBS interactions are similar but 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 electron microscopy, checkpoint/CIN assays with interface mutants 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 and not other dynein light chains; Bub3 thereby interacts with the cytoplasmic dynein complex. DYNLT3 localizes to kinetochores at prometaphase and is depleted upon chromosome alignment. Knockdown of DYNLT3 increases mitotic index, particularly cells in prophase/prometaphase. GST pull-down, co-immunoprecipitation, immunofluorescence, siRNA knockdown The Journal of biological chemistry Medium 17289665
2008 Human Bub3 is required for the establishment of correct kinetochore-microtubule (K-MT) attachments; Bub3 depletion by RNAi causes defective K-MT attachments with misaligned chromosomes predominantly in side-on configuration. Aurora B inhibition exacerbates alignment defects in Bub3-depleted cells, distinguishing Bub3's role from that of BubR1. RNA interference, high-resolution microscopy, Aurora B kinase inhibitor treatment Molecular biology of the cell Medium 18199686
2009 BUB3 dissociates from BUB1 under partial BUB1 depletion conditions; the freed BUB3 associates specifically with p73 (phosphorylated at Y99 by c-Abl tyrosine kinase), leading to activation of caspase-independent mitotic death (CIMD). This interaction was detected only in cells undergoing CIMD. Co-immunoprecipitation, siRNA knockdown, CIMD assay Cell death and differentiation Medium 20057499
2012 In fission yeast, the Mps1 kinase (Mph1) phosphorylates conserved MELT motifs in Spc7/KNL1, and this phosphorylation recruits Bub1 and Bub3 to the kinetochore, which is required to maintain the SAC signal. Phospho-specific analysis, mutant MELT motif analysis, checkpoint assay in fission yeast Current biology : CB High 22521786
2013 Bub3 is the direct reader of phosphorylated MELT motifs (MELTp) on the kinetochore subunit Spc105/Knl1. Bub3's exceptionally conserved interface on the side of its β-propeller docks the MELTp sequence. Mutations targeting this interface prevent kinetochore recruitment of the SAC kinase Bub1 and cause a checkpoint defect. Structural analysis (crystallography-guided), mutagenesis of Bub3 interface, kinetochore recruitment assay, checkpoint assay eLife High 24066227
2014 BuGZ (ZNF207) directly binds and stabilizes Bub3 through a conserved GLEBS domain. BuGZ also uses its microtubule-binding domain to enhance loading of Bub3 to kinetochores during prometaphase. Inhibition of BuGZ results in loss of both Bub3 and Bub1 from kinetochores, reduced Bub1-dependent H2A phosphorylation, attenuated Aurora B activity, and chromosome congression defects. Co-immunoprecipitation, direct binding assay, RNAi, rescue with BuGZ mutants, immunofluorescence Developmental cell High 24462186 24462187
2014 Bub3 promotes mitotic checkpoint signaling via two distinct mechanisms: (1) at unattached kinetochores, Bub3 facilitates BubR1 binding and Cdc20 recruitment to kinetochores via BubR1's internal Cdc20-binding site; (2) downstream of kinetochores, Bub3 promotes binding of BubR1's N-terminal Cdc20-binding domain to a site in Cdc20 exposed by prior Mad2 binding, generating the final inhibitory MCC (Bub3-BubR1-Cdc20) that selectively inhibits APC/C-Cdc20. In vitro reconstitution of MCC, cell-based checkpoint assays, biochemical fractionation Proceedings of the National Academy of Sciences of the United States of America High 25246557
2015 Human KNL1 contains 19 MELT-like repeats, of which only a limited number are 'active.' Active repeats contain a vertebrate-specific SHT motif C-terminal to MELT. MPS1 phosphorylates SHT only after prior MELT phosphorylation; phospho-SHT (SHpT) synergizes with MELpT for BUB3/BUB1 binding in vitro and in cells. BUB3 mutated at a predicted SHpT-binding surface cannot localize to kinetochores, demonstrating sequential multisite phospho-regulation of the KNL1-BUB3 interface. Systematic mutational screening, in vitro binding assays, cell-based kinetochore recruitment assay, BUB3 mutagenesis Molecular cell High 25661489
2015 BUB3 acts in promoting Cdc20-dependent APC/C activation for normal metaphase progression in budding yeast; loss of Bub3 causes a metaphase delay (not due to checkpoint activation or aneuploidy), impairs APC/C–Cdc20 binding, and is rescued by Cdc20 overexpression. Kinetochore localization of Bub3 is required for this function. Bub3 deletion in budding yeast, Cdc20 overexpression rescue, APC/C co-immunoprecipitation, kinetochore localization assay The Journal of cell biology Medium 25987604
2015 In Drosophila, Bub3–BubR1 complex on broken chromosomes is required for BubR1 localization to broken fragments and for proper segregation of broken chromosomes; Cdc20/Fizzy accumulates on DNA breaks in a BubR1 KEN-box-dependent manner, and the Bub3-BubR1 complex locally inhibits APC/C via Cdc20 sequestration to promote transmission of broken chromosomes. Co-immunoprecipitation, immunofluorescence, APC/C biosensor, genetic mutant analysis The Journal of cell biology Medium 26553926
2015 A motif from Lys216 to Lys222 in human BUB3 is its nuclear localization signal. A deletion mutant (Del216–222) mislocalizes to cytoplasm and fails to localize to kinetochores; mutant BUB3 cannot mediate mitotic checkpoint arrest. The mutant retains interaction with BUB1, MAD2, and BubR1 but has impaired association with centromeric components CENP-A region and KNL1. Deletion and point mutagenesis, subcellular localization by fluorescence microscopy, co-immunoprecipitation, checkpoint assay The Journal of biological chemistry Medium 25814666
2016 In fission yeast, multisite binding of Bub3 to the Spc7 MELT array toggles the spindle checkpoint switch by permitting Mph1 (Mps1)-dependent interaction of Bub1 with Mad1-Mad2. Genetic and biochemical analysis in fission yeast, phospho-MELT mutant analysis, co-immunoprecipitation Current biology : CB Medium 27618268
2016 The Bub3–BubR1 interaction is a high-affinity, 1:1, enthalpy-driven, slow-dissociation event dependent on the BubR1 GLEBS motif. Disruption of endogenous BubR1–Bub3 complexes phenocopies BUB3 knockdown (abrogated SAC, apoptosis, reduced proliferation). N- and C-terminal regions flanking the GLEBS motif modulate binding affinity and kinetics as 'hotspots'. Surface plasmon resonance, isothermal titration calorimetry, knockdown, peptide competition assay The Journal of biological chemistry High 27030009
2017 The BubR1 'loop' region directs Bub3 to different phosphorylated targets from those recognized via the Bub1 loop; BubR1 loop mutants bind Bub3 and incorporate into MCC in vitro normally but have reduced ability to inhibit APC/C, indicating that BubR1:Bub3 recognition/inhibition of APC/C requires phosphorylation. The Bub1 loop cannot substitute for the BubR1 loop in SAC function. In vitro MCC reconstitution, APC/C inhibition assay, mutant analysis in cells Current biology : CB High 28943088
2018 The BUB3-BUB1 complex binds to telomeres during S phase and promotes telomere DNA replication; loss of the complex leads to telomere replication defects (fragile and shortened telomeres). TRF2 targets BUB1-BUB3 to telomeres. BUB1 kinase activity phosphorylates TRF1 to promote TRF1 recruitment of BLM helicase. The telomere-binding ability of BUB3 and kinase activity of BUB1 are each required. ChIP, telomere FISH, co-immunoprecipitation, kinase assay, domain/kinase-dead mutant analysis Molecular cell High 29727616
2020 The RepID-CRL4 ubiquitin ligase complex triggers SAC termination by ubiquitinating BUB3, enabling mitotic exit. During interphase, BUB3 is protected from CRL4-mediated degradation by association with PML nuclear bodies, ensuring availability at mitotic onset. CRL4 replaces RepID with RBBP7 during mitosis to ubiquitinate BUB3. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, cell fractionation, mitotic timing assay Nature communications Medium 31911655
2020 In budding yeast meiosis, Bub3 is crucial for correction of chromosome attachment errors; loss of Bub3 reduces kinetochore-localized Aurora B/Ipl1 levels and causes massive chromosome missegregation. Bub3 depletion also causes premature PP1 localization to kinetochores (antagonizing Ipl1 phosphorylation) and shorter metaphase I and II, establishing a role for the Bub1-Bub3 pathway in balancing Ipl1 and PP1 at kinetochores. Conditional Bub3 depletion in yeast meiosis, immunofluorescence, kinetochore tension assay The Journal of cell biology Medium 32328625
2021 EZH2 methylates FOXA1 at lysine-295; this methyl-mark is recognized by BUB3's WD40 repeat domain, which subsequently recruits USP7 deubiquitinase to remove ubiquitination and stabilize FOXA1 protein, promoting prostate cancer cell growth. Co-immunoprecipitation, methylation assay, ubiquitination assay, domain mutant analysis, cancer cell growth assay Science advances Medium 33827814
2022 ATM kinase phosphorylates Bub3 on serine 135 (Ser135) both in vitro and in vivo, validated by SILAC-MS. During mitosis, this phosphorylation promotes activation of Bub1 (SAC activation); mutation of Ser135 to alanine causes SAC defect. In response to ionizing radiation, the same ATM-mediated Bub3 Ser135 phosphorylation promotes interaction with the Ku70-Ku80-DNA-PKcs complex and efficient NHEJ repair. SILAC mass spectrometry, in vitro kinase assay, phospho-site mutagenesis, checkpoint assay, DNA repair assay The Journal of biological chemistry High 35085551
2021 Fin1-PP1 promotes removal of Bub3 (and its partner Bub1) from kinetochores during anaphase in budding yeast by dephosphorylating the Aurora B/Ipl1 substrate Ndc80; Aurora B activity is required for Bub1-Bub3 kinetochore localization during anaphase, and untimely Ndc80 dephosphorylation causes viability loss under tensionless attachment conditions. Genetic analysis in budding yeast, phospho-Ndc80 assay, kinetochore localization by fluorescence microscopy PLoS genetics Medium 34033659
2018 Mitotic arrest induces p38-dependent phosphorylation of Bub3 at Ser211, which promotes interaction between Bub3 and DMAP1; the resulting DMAP1/Bub3 complex is recruited by TAp73 to the BCL2L1 promoter, mediating DNA methylation and repression of anti-apoptotic gene transcription. c-Src phosphorylates DMAP1 at Tyr246, which impedes DMAP1/Bub3 interaction and thereby blocks apoptosis in pancreatic cancer cells. Co-immunoprecipitation, phospho-site mutant analysis, chromatin immunoprecipitation, reporter assay, in vivo tumor model Molecular cancer Medium 30553276
2022 In PAH pulmonary arterial smooth muscle cells, MST1/2 forms a disease-specific interaction with BUB3 and supports ECM- and USP10-dependent BUB3 accumulation, upregulation of Akt-mTORC1, cell proliferation, and survival. Proteomic analysis, co-immunoprecipitation, gain/loss-of-function, pharmacological inhibition Circulation research Low 35124974
2023 The SETD1A FLOS domain binds BuGZ/BUB3 mitosis-associated proteins; BuGZ/BUB3 localize to SETD1A-bound promoter-TSS regions and SETD1A-negative H3K4me1-positive enhancer regions. Inhibition of both cyclin K and BuGZ/BUB3-binding motifs in SETD1A shows synergistic antileukemic effects. The GLEBS motif and intrinsically disordered region of BuGZ are required for SETD1A binding. Co-immunoprecipitation, ChIP-seq, domain mutant analysis, cell viability assay EMBO reports Low 37535603
2014 USP7 interacts with Bub3 and acts as a deubiquitinase to stabilize Bub3; USP7 depletion decreases Bub3 levels, resulting in prolonged mitosis and mitotic abnormalities including lagging chromosomes. Co-immunoprecipitation, USP7 depletion by siRNA/inhibitor, Western blot for Bub3 levels Oncotarget Medium 25003721
2009 In Xenopus egg extracts, Bub1 is required for kinetochore localization of Bub3, and both exist as constitutive complexes throughout the cell cycle; Bub3 requires Bub1 for recruitment to kinetochores, consistent with mammalian data. Immunoprecipitation from Xenopus egg extracts, localization studies in oocytes PloS one Medium 19888327
2009 TAp73alpha, but not p53 or other p73 isoforms, physically binds Bub1 and Bub3 in cells, and overexpression of TAp73alpha induces polyploidy, suggesting interference with mitotic checkpoint function. Co-immunoprecipitation, overexpression, ploidy analysis Cell cycle (Georgetown, Tex.) Low 19182530
2020 Wapl interacts with Bub3 (identified by co-immunoprecipitation and mass spectrometry) and controls SAC activity by maintaining Bub3 protein levels in mouse oocytes; exogenous Bub3 rescues the meiotic defects caused by Wapl depletion. Co-immunoprecipitation, mass spectrometry, RNAi, rescue by Bub3 overexpression Science advances Medium 32284991
2023 The Bub1-Bub3 complex controls fasting-induced lipid catabolism in the Drosophila fat body; bidirectional deviations of Bub1 or Bub3 levels affect triacylglycerol consumption and adult fly survival under starvation. Bub1 and Bub3 attenuate lipid degradation via macrolipophagy upon fasting. Genetic manipulation (overexpression/RNAi) of Bub1 and Bub3 in Drosophila fat body, lipid staining, survival assay Cell reports Medium 37027296

Source papers

Stage 0 corpus · 79 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 242 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 190 24066227
2001 Bub3 interaction with Mad2, Mad3 and Cdc20 is mediated by WD40 repeats and does not require intact kinetochores. The EMBO journal 160 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 106 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 101 12011073
2015 Sequential multisite phospho-regulation of KNL1-BUB3 interfaces at mitotic kinetochores. Molecular cell 95 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 82 24462186
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 80 12217960
1998 Localization of the Drosophila checkpoint control protein Bub3 to the kinetochore requires Bub1 but not Zw10 or Rod. Chromosoma 80 9914369
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
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
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 62 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 52 23609535
2001 Molecular analysis of the mitotic checkpoint genes BUB1, BUBR1 and BUB3 in human lung cancers. Cancer letters 51 11146226
2022 Noncanonical HIPPO/MST Signaling via BUB3 and FOXO Drives Pulmonary Vascular Cell Growth and Survival. Circulation research 46 35124974
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
2007 The DYNLT3 light chain directly links cytoplasmic dynein to a spindle checkpoint protein, Bub3. The Journal of biological chemistry 40 17289665
2017 BubR1 Promotes Bub3-Dependent APC/C Inhibition during Spindle Assembly Checkpoint Signaling. Current biology : CB 39 28943088
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 32 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
2015 Bub3-BubR1-dependent sequestration of Cdc20Fizzy at DNA breaks facilitates the correct segregation of broken chromosomes. The Journal of cell biology 24 26553926
2010 BUB3 that dissociates from BUB1 activates caspase-independent mitotic death (CIMD). Cell death and differentiation 24 20057499
2015 Bub3 promotes Cdc20-dependent activation of the APC/C in S. cerevisiae. The Journal of cell biology 23 25987604
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
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
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
2020 Differential requirement for Bub1 and Bub3 in regulation of meiotic versus mitotic chromosome segregation. The Journal of cell biology 20 32328625
2021 The long noncoding RNA CRYBG3 induces aneuploidy by interfering with spindle assembly checkpoint via direct binding with Bub3. Oncogene 19 33564066
2014 Usp7 protects genomic stability by regulating Bub3. Oncotarget 19 25003721
2003 Analysis of Bub3 spindle checkpoint function in Xenopus egg extracts. Journal of cell science 18 12538762
2022 BUB3, beyond the Simple Role of Partner. Pharmaceutics 17 35631670
2020 The cohesin release factor Wapl interacts with Bub3 to govern SAC activity in female meiosis I. Science advances 16 32284991
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
2024 YY2/BUB3 Axis promotes SAC Hyperactivation and Inhibits Colorectal Cancer Progression via Regulating Chromosomal Instability. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 15 38682484
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
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 12 30553276
2016 Functional and Structural Characterization of Bub3·BubR1 Interactions Required for Spindle Assembly Checkpoint Signaling in Human Cells. The Journal of biological chemistry 12 27030009
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
2022 Research progress of Bub3 gene in malignant tumors. Cell biology international 8 34882895
2023 Bub1 and Bub3 regulate metabolic adaptation via macrolipophagy in Drosophila. Cell reports 7 37027296
2015 In situ carcinoma developed over oral lichen planus: a case report with analysis of BUB3, p16, p53, Ki67 and SOX4 expression. Journal of applied oral science : revista FOB 7 26398519
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
2016 Zfp207 is a Bub3 binding protein regulating meiotic chromosome alignment in mouse oocytes. Oncotarget 6 27177335
2015 A motif from Lys216 to Lys222 in human BUB3 protein is a nuclear localization signal and critical for BUB3 function in mitotic checkpoint. The Journal of biological chemistry 6 25814666
2015 Co-silencing of human Bub3 and dynein highlights an antagonistic relationship in regulating kinetochore-microtubule attachments. FEBS letters 6 26526612
2014 A protective chaperone for the kinetochore adaptor Bub3. Developmental cell 6 24525184
2022 Arrest of Cell Cycle by Avian Reovirus p17 through Its Interaction with Bub3. Viruses 5 36366482
2025 Aneuploidy of specific chromosomes is beneficial to cells lacking spindle checkpoint protein Bub3. PLoS genetics 3 39903784
2022 A role for the mitotic proteins Bub3 and BuGZ in transcriptional regulation of catalase-3 expression. PLoS genetics 3 35666721
2020 [Expression and clinical significance of Spindly and Bub3 in oral squamous cell carcinoma]. Shanghai kou qiang yi xue = Shanghai journal of stomatology 3 33543222
2025 mir-188-5p emerges as an oncomir to promote chronic myeloid leukemia via upregulation of BUB3 and SUMO2. Molecular biology reports 1 40019654
2026 NUF2 interacts with BUB3 and drives lung adenocarcinoma progression through activation of the NF-κB pathway. World journal of surgical oncology 0 41943078
2024 Aneuploidy of Specific Chromosomes is Beneficial to Cells Lacking Spindle Checkpoint Protein Bub3. bioRxiv : the preprint server for biology 0 39282354
2023 Analysis of Bub3 and Nup75 in the Drosophila male germline lineage. Cells & development 0 37286104
2018 Publisher Correction: Role of the BUB3 protein in phragmoplast microtubule reorganization during cytokinesis. Nature plants 0 30087424
2006 [Abnormal promoter methylation of p14(ARF), p16(INK4a)and BUB3 genes in malignant transformed cells induced by radiation]. Zhongguo fei ai za zhi = Chinese journal of lung cancer 0 21172153

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