Affinage

BAP1

Ubiquitin carboxyl-terminal hydrolase BAP1 · UniProt Q92560

Length
729 aa
Mass
80.4 kDa
Annotated
2026-04-28
100 papers in source corpus 35 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BAP1 is a nuclear deubiquitinase that serves as the catalytic subunit of the Polycomb repressive deubiquitinase (PR-DUB) complex, coupling histone H2AK119Ub removal with transcriptional regulation, DNA repair, replication fork progression, calcium-mediated apoptosis, and ferroptosis. Activated by ASXL1/2/3 DEUBAD domains that generate a composite ubiquitin-binding interface conferring specificity for H2AK119Ub over DNA-damage-associated H2AK13/15Ub, BAP1 restructures the nucleosome to access its substrate, as revealed by cryo-EM (PMID:37556531, PMID:26739236). Beyond histones, BAP1 deubiquitinates and stabilizes diverse protein substrates—including HCF-1, IP3R3 at the ER (promoting Ca²⁺ flux and apoptosis), INO80 (enabling replication fork restart), PTEN, KLF5, and HDAC1—thereby integrating chromatin remodeling with cell proliferation, genomic stability, and metabolic control (PMID:19815555, PMID:28614305, PMID:25283999, PMID:33155366, PMID:26419610, PMID:34815344). BAP1 represses SLC7A11 transcription through H2Aub removal to restrict cystine uptake and sensitize cells to ferroptosis, and its nuclear import is governed by transportin-1 recognition of a C-terminal PY-NLS that competes with UBE2O-mediated cytoplasmic retention, while its stability is modulated by glutamylation at Glu651 (PMID:30202049, PMID:35446349, PMID:31699823).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2009 High

    Identifying HCF-1 as a direct BAP1 substrate established that BAP1 functions as a deubiquitinase for non-histone proteins with roles in cell proliferation, not solely as a chromatin modifier.

    Evidence Mass spectrometry, reciprocal Co-IP, in vitro DUB assay, and HBM-mutant functional analysis in human cells

    PMID:19815555

    Open questions at the time
    • Whether HCF-1 deubiquitination is the primary mechanism of BAP1 tumor suppression was unresolved
    • Full repertoire of BAP1 substrates unknown
  2. 2010 High

    Mapping BAP1 inactivating mutations to the UCH catalytic domain in metastasizing uveal melanomas established that deubiquitinase activity is essential for BAP1's tumor-suppressive function.

    Evidence Exome sequencing of uveal melanomas with mutation mapping to the UCH domain

    PMID:21051595

    Open questions at the time
    • The critical substrate(s) mediating tumor suppression were not identified
    • Whether catalytic activity is the sole tumor-suppressive mechanism was unclear
  3. 2012 High

    Demonstrating that HCF-1 binding and H2AK119Ub deubiquitination are separable BAP1 functions revealed that BAP1 tumor suppression involves multiple independent downstream pathways.

    Evidence Tumorgraft fractionation, HBM-mutant analysis distinguishing proliferation control from H2A DUB activity in renal cell carcinoma

    PMID:22683710

    Open questions at the time
    • Relative contributions of H2A DUB versus HCF-1 DUB to tumor suppression in different cancer types unclear
  4. 2013 High

    Showing that BAP1 is recruited to DSB sites and that both catalytic activity and IR-induced phosphorylation are required for HR-mediated repair placed BAP1 in the DNA damage response and revealed phosphorylation as a regulatory input.

    Evidence DT40 knockout, immunofluorescence foci, ChIP at I-SceI sites, phospho-site mutagenesis

    PMID:24347639

    Open questions at the time
    • Identity of the kinase(s) phosphorylating BAP1 after IR not determined
    • Precise DUB substrate at DSBs not identified
  5. 2014 High

    Identification of INO80 as a BAP1 substrate that is stabilized by deubiquitination and recruited to replication forks extended BAP1 function from transcription and repair to DNA replication fork progression.

    Evidence Co-IP, in vitro DUB assay, ChIP at replication forks in BAP1-defective cancer cells

    PMID:25283999

    Open questions at the time
    • How BAP1 senses replication stress to recruit INO80 was not defined
  6. 2015 High

    Biochemical reconstitution showing that ASXL1/2 DEUBAD domains form a composite ubiquitin-binding interface with BAP1 and activate H2AK119Ub-specific (but not H2AK13/15Ub) deubiquitination defined the PR-DUB activation mechanism and its substrate selectivity.

    Evidence In vitro reconstitution with purified proteins, nucleosome-binding assays, domain deletion/mutation analysis

    PMID:26416890 PMID:26739236

    Open questions at the time
    • Structural basis for selectivity between H2AK119Ub and H2AK13/15Ub not resolved at atomic level
  7. 2015 High

    Genetic epistasis between Bap1 loss and Ezh2 deletion in mice revealed that BAP1 indirectly opposes PRC2-mediated H3K27me3 through effects on H4K20me1 and EZH2 levels, placing BAP1 in a Polycomb regulatory circuit.

    Evidence Bap1/Ezh2 double conditional KO mice, ChIP-seq for H3K27me3 and H4K20me1, pharmacological EZH2 inhibition

    PMID:26437366

    Open questions at the time
    • Whether BAP1 directly or indirectly controls EZH2 expression levels was not resolved
  8. 2017 High

    Discovery that BAP1 localizes to the ER where it deubiquitinates and stabilizes IP3R3 to promote Ca²⁺-mediated apoptosis established a non-chromatin tumor-suppressive mechanism operating through calcium signaling.

    Evidence Subcellular fractionation, ER imaging, DUB assay, Ca²⁺ flux measurement, BAP1+/− patient-derived cells

    PMID:28614305

    Open questions at the time
    • How BAP1 partitions between nucleus and ER was not mechanistically explained
    • ER-specific interactors beyond IP3R3 not catalogued
  9. 2018 High

    Demonstration that BAP1 represses SLC7A11 by removing H2Aub at its promoter, thereby restricting cystine uptake and sensitizing cells to ferroptosis, linked BAP1's epigenetic activity to a specific regulated cell death pathway.

    Evidence ChIP-seq for H2Aub, RNA-seq, ferroptosis and lipid peroxidation assays, catalytic mutant analysis, xenograft models

    PMID:30202049

    Open questions at the time
    • Whether ferroptosis contributes to BAP1's tumor-suppressive activity in patients was not established
  10. 2018 High

    Finding that truncated ASXL1 gain-of-function mutants increase BAP1 stability, chromatin recruitment, and H2AK119Ub removal at HOXA loci to drive myeloid leukemogenesis revealed how oncogenic ASXL1 mutations hijack normal PR-DUB activity.

    Evidence Co-IP, ChIP-seq for H2AK119ub, in vivo leukemia models, BAP1 catalytic inhibitor validation

    PMID:30013160 PMID:35122023

    Open questions at the time
    • Whether BAP1 catalytic inhibitors are therapeutically viable in ASXL1-mutant leukemia patients not tested clinically
  11. 2020 High

    Identification of glutamylation at Glu651 as a degradation signal for BAP1—installed by TTLL5/7 and removed by CCP3—revealed a novel post-translational regulatory layer controlling BAP1 stability in hematopoietic stem cells.

    Evidence In vitro glutamylation/deglutamylation assays, BAP1-E651A knock-in mice, CCP3 KO mice

    PMID:31699823

    Open questions at the time
    • Whether glutamylation regulates BAP1 in non-hematopoietic tissues is unknown
    • Identity of the E3 ligase triggered by glutamylation not determined
  12. 2020 High

    Expanding BAP1's substrate repertoire to include PTEN established a direct link between BAP1 deubiquitinase activity and suppression of PI3K-AKT signaling in cancer.

    Evidence Reciprocal Co-IP, in vitro DUB assay on PTEN, AKT pathway readouts, xenograft rescue with PTEN re-expression

    PMID:33155366

    Open questions at the time
    • Whether PTEN stabilization is relevant across all BAP1-mutant cancer types or tissue-specific
  13. 2022 High

    Mapping transportin-1 recognition of BAP1's PY-NLS and its competition with UBE2O-mediated monoubiquitination explained how BAP1 nuclear-cytoplasmic distribution is actively regulated, resolving the question of how BAP1 partitions between nuclear and ER functions.

    Evidence Biochemical binding assays, nuclear import assays, PY-NLS mutagenesis, UBE2O competition assay

    PMID:35446349

    Open questions at the time
    • Signal(s) that shift the TNPO1–UBE2O balance in physiological or stress contexts not identified
  14. 2023 High

    The cryo-EM structure of BAP1–ASXL1 DEUBAD bound to H2AK119Ub nucleosome resolved at atomic detail how PR-DUB achieves substrate specificity by restructuring the nucleosome, and structurally rationalized >50 cancer mutations.

    Evidence Cryo-EM structure determination, biochemical reconstitution, cellular DUB assays, cancer mutation mapping

    PMID:37556531

    Open questions at the time
    • Structures with ASXL2 or ASXL3 not determined
    • How the PR-DUB complex is recruited to specific genomic loci rather than acting genome-wide remains unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BAP1 is targeted to specific genomic loci (beyond FoxK2- and YY1-mediated recruitment) to achieve gene-selective H2AK119Ub removal, and how its nuclear versus ER functions are coordinately regulated under physiological conditions, remain major open questions.
  • Genome-wide determinants of BAP1 locus specificity not systematically defined
  • Relative contributions of chromatin vs. ER-based tumor suppression not quantified in vivo
  • Whether BAP1 catalytic inhibitors represent viable cancer therapeutics is untested clinically

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 12 GO:0140096 catalytic activity, acting on a protein 8 GO:0042393 histone binding 3
Localization
GO:0005634 nucleus 8 GO:0005694 chromosome 3 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-4839726 Chromatin organization 9 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-162582 Signal Transduction 2 R-HSA-1640170 Cell Cycle 2 R-HSA-69306 DNA Replication 2 R-HSA-73894 DNA Repair 2 R-HSA-168256 Immune System 1
Partners
ASXL1ASXL2ASXL3FOXK2HCF1INO80TNPO1YY1
Complex memberships
BAP1-HMGB1-HDAC1 complexDRED γ-globin repressor complexPR-DUB (Polycomb repressive deubiquitinase)

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 BAP1 contains a ubiquitin carboxyl-terminal hydrolase (UCH) domain, and inactivating mutations including those affecting this UCH domain are found in metastasizing uveal melanomas, implicating BAP1 deubiquitinase activity in tumor suppression. Exome capture and massively parallel sequencing; mutation mapping to functional domain Science High 21051595
2009 BAP1 interacts with and deubiquitinates host cell factor-1 (HCF-1) via a dedicated HCF-1 binding motif (HBM), and this interaction is required for BAP1-mediated cell proliferation regulation; HCF-1N is modified with Lys-48-linked polyubiquitin on its Kelch domain, which BAP1 removes. Mass spectrometry of co-purified proteins, Co-IP, in vitro deubiquitination assay, RNAi, dominant-negative overexpression The Journal of Biological Chemistry High 19815555
2012 BAP1 co-fractionates with and binds HCF-1 in renal cell carcinoma tumorgrafts; mutations disrupting the HCF-1 binding motif impair BAP1-mediated suppression of cell proliferation but not deubiquitination of H2AK119ub1, indicating separable functions. Tumorgraft fractionation, Co-IP, cell proliferation assays, H2AK119ub1 deubiquitination assay, domain mutation analysis Nature Genetics High 22683710
2013 BAP1 is required for efficient assembly of homologous recombination factors BRCA1 and RAD51 at ionizing radiation-induced foci; BAP1 is recruited to DSB sites, and both its catalytic activity and IR-induced phosphorylation at six sites are critical for DSB repair by HR. RNAi screen, DT40 knockout cells, immunofluorescence foci assay, ChIP at I-SceI DSB site, phosphorylation site mutagenesis PNAS High 24347639
2014 BAP1 deubiquitinates and stabilizes INO80 (catalytic ATPase of the INO80 chromatin-remodelling complex) and recruits it to replication forks via ubiquitinated H2A, promoting replication fork progression during normal DNA synthesis. Co-IP, in vitro deubiquitination assay, ChIP at replication forks, BAP1-defective cancer cell lines, mouse embryo Ino80 knockout Nature Communications High 25283999
2014 BAP1 acts as a deubiquitinase for histone H2A and is recruited to FoxK2 target gene promoters through an interaction with the forkhead-associated domain of FoxK2 (which binds phospho-Thr493 on BAP1); BAP1 bridges FoxK2 and HCF-1 in a ternary complex and represses FoxK2 target genes in opposition to the Ring1B-Bmi1 E3 ligase. ChIP, Co-IP, reporter assays, phospho-specific interaction mapping, RNAi knockdown The Journal of Biological Chemistry High 25451922
2015 BAP1 forms two mutually exclusive complexes with ASXL1 and ASXL2 via their ASXM domains interacting with BAP1's C-terminal domain (CTD); these interactions generate a composite ubiquitin-binding interface (CUBI) required for H2AK119 deubiquitination, and ASXL2 interaction also regulates cell senescence. Co-IP, in vitro deubiquitination assay, cancer-associated mutation analysis, cell proliferation and senescence assays The Journal of Biological Chemistry High 26416890
2015 BAP1 acts as a bona fide deubiquitinase for KLF5 transcription factor in breast cancer cells, directly interacting with KLF5 and stabilizing it by removing ubiquitin; KLF5 is a component of the BAP1/HCF-1 complex, which promotes cell cycle progression partly by inhibiting p27 expression. Genome-wide siRNA DUB screen, Co-IP, in vitro deubiquitination assay, rescue experiments with KLF5 re-expression, xenograft models Nature Communications High 26419610
2015 Loss of BAP1 results in decreased H4K20 monomethylation (H4K20me1) and increased H3K27me3 via upregulation of EZH2; conditional co-deletion of Bap1 and Ezh2 in mice abrogates myeloid progenitor expansion caused by Bap1 loss alone, placing BAP1 upstream of the EZH2/PRC2 pathway. Mouse conditional knockout (Bap1/Ezh2 double KO), ChIP-seq (H3K27me3, H4K20me1), pharmacological EZH2 inhibition Nature Medicine High 26437366
2016 BAP1's C-terminal extension auto-recruits BAP1 to nucleosomes independently of the acidic patch; the DEUBAD domains of ASXL1, ASXL2, or ASXL3 then activate BAP1 by increasing its affinity for ubiquitin on H2A to drive deubiquitination specifically of H2AK119Ub (Polycomb modification) but not H2AK13/15Ub (DNA damage modification). In vitro reconstituted deubiquitination assay with purified proteins, nucleosome-binding assays, domain deletion/mutation analysis Nature Communications High 26739236
2017 BAP1 localizes to the endoplasmic reticulum (ER), where it binds, deubiquitylates, and stabilizes the type 3 inositol-1,4,5-trisphosphate receptor (IP3R3), thereby modulating Ca2+ release from the ER into the cytosol and mitochondria and promoting apoptosis; reduced BAP1 in BAP1+/- carriers decreases IP3R3 levels and Ca2+ flux, preventing apoptosis after genotoxic stress. Subcellular fractionation, ER localization imaging, Co-IP, in vitro deubiquitination assay, Ca2+ flux measurements, BAP1+/- patient cell lines, cellular transformation assays Nature High 28614305
2017 BAP1 decreases H2Aub occupancy at the SLC7A11 (cystine transporter) promoter and represses SLC7A11 expression in a deubiquitinating-dependent manner, inhibiting cystine uptake and leading to elevated lipid peroxidation and ferroptosis; cancer-associated BAP1 mutants lose ability to repress SLC7A11 and promote ferroptosis. ChIP-seq (H2Aub), RNA-seq, CRISPR/siRNA knockdown, ferroptosis assays, lipid peroxidation measurement, xenograft tumor models Nature Cell Biology High 30202049
2017 BAP1 inhibits glucose deprivation-induced cell death by repressing the metabolic stress UPR transcriptional network through binding to and inhibiting transcription of ATF3 and CHOP promoters, dependent on its deubiquitinating activity; Bap1 KO mice show enhanced sensitivity to tunicamycin-induced renal damage. ChIP, reporter assays, RNAi, Bap1 KO mice, metabolic stress assays (ROS, ATP measurements) PNAS High 28275095
2018 BAP1 is a component of the DRED γ-globin gene repressor complex and maintains NCoR1 at sites in the β-globin locus through deubiquitinase activity; BAP1 inhibition in erythroid cells massively induces γ-globin synthesis. Co-IP, ChIP, BAP1 inhibition in erythroid cells, γ-globin expression assays Genes & Development High 30463901
2018 Truncated ASXL1 (gain-of-function frameshift mutant) increases BAP1 protein stability and enhances BAP1 recruitment to chromatin, promoting pro-leukemic transcriptional signatures; BAP1 catalytic inhibitors suppress truncated-ASXL1-driven leukemic gene expression and impair tumor progression in vivo. Biochemical screen for BAP1 inhibitors, western blot, ChIP-seq, in vivo leukemia models Nature Cancer High 35122023
2018 Mutant ASXL1 (C-terminal truncation) increases BAP1's catalytic function via monoubiquitination of ASXL1-MT; the hyperactive ASXL1-MT/BAP1 complex drives myeloid leukaemogenesis by removing H2AK119 ubiquitination at posterior HOXA genes and IRF8, upregulating their expression. Co-IP, in vitro ubiquitination/deubiquitination assays, ChIP-seq (H2AK119ub), gene expression analysis, mouse leukemia models Nature Communications High 30013160
2019 BAP1 promotes restart of hydroxyurea-induced stalled replication forks by recruiting INO80 to stalled forks; BAP1 depletion abrogates INO80 binding at stalled forks, increases RAD51 foci, reduces S-phase progression under replication stress, and causes hypersensitivity to HU, all rescued by INO80 re-expression. DNA fiber assay, iPOND/ChIP at stalled forks, immunofluorescence, INO80 rescue expression, HU sensitivity assays The Biochemical Journal High 31657441
2020 BAP1 deubiquitinates and stabilizes PTEN protein; BAP1 physically binds PTEN, removes ubiquitin from PTEN to prevent proteasomal degradation, increases PTEN protein levels, and thereby inhibits AKT signaling and prostate cancer progression. Co-IP, in vitro deubiquitination assay, BAP1 knockdown/overexpression, AKT pathway readouts, xenograft rescue with PTEN re-expression Molecular Oncology High 33155366
2020 BAP1 depletion causes proteasome-mediated degradation of BRCA1 in mesothelioma cells; BAP1 loss leads to spindle assembly checkpoint failure, centrosome amplification, and chromosome segregation errors (BRCA1-dependent), plus increased spindle length and astral microtubule growth due to loss of KIF18A and KIF18B kinesins (BRCA1-independent). BAP1 siRNA depletion, BRCA1 immunoblot with proteasome inhibitor rescue, immunofluorescence mitotic phenotypes, KIF18A/B re-expression rescue Oncogene High 36550359
2020 BAP1 depletion in pancreatic cancer leads to enhanced ubiquitin-dependent proteasomal degradation of the Hippo pathway tumor suppressor LATS, deregulating the Hippo pathway and promoting tumor progression. Conditional Bap1 knockout in KrasG12D pancreatic cancer mouse model, LATS ubiquitination/stability assays, Hippo pathway readouts Cancer Research Medium 31988076
2020 BAP1 is glutamylated at Glu651 by TTLL5 and TTLL7, and this glutamylation accelerates BAP1 ubiquitination and proteasomal degradation; the carboxypeptidase CCP3 removes glutamylation from BAP1 to stabilize it, enhancing Hoxa1 expression and promoting HSC self-renewal. In vitro glutamylation/deglutamylation assays, ubiquitination assays, CCP3 KO mice, BAP1-E651A knock-in mice, gene expression analysis The Journal of Experimental Medicine High 31699823
2021 BAP1 forms a trimeric protein complex with HMGB1 and HDAC1; reduced BAP1 levels cause increased ubiquitylation and degradation of HDAC1, leading to increased HMGB1 acetylation and its active secretion, which promotes mesothelial cell transformation. Co-IP (trimeric complex identification), ubiquitination assay for HDAC1, HMGB1 acetylation measurement, secretion assay, BAP1+/- patient serum analysis PNAS High 34815344
2021 BAP1 downregulation is required to trigger epithelial-mesenchymal transition (EMT) during trophoblast differentiation; this function depends on BAP1 binding to ASXL1/2 proteins to form the PR-DUB complex, as demonstrated by CRISPR knockout and overexpression in mouse and human trophoblast stem cells. CRISPR/Cas9 KO, BAP1 overexpression, EMT marker analysis, BAP1-ASXL1/2 interaction studies in trophoblast stem cells eLife High 34170818
2021 BAP1 cell-intrinsically regulates B lymphocyte development by deubiquitinating histone H2AK119ub; Bap1 conditional deletion in B cells depletes large pre-B cells, transitional, and mature B cells, with broad transcriptional changes mapped by BAP1 ChIP-seq and H2AK119ub profiling. Bap1fl/fl mb1-Cre conditional KO mice, flow cytometry, RNA-seq, ChIP-seq (BAP1 binding, H2AK119ub) Frontiers in Immunology High 33912157
2021 BAP1 negatively regulates expression of TRAIL receptors DR4 and DR5 through direct interaction with the transcription factor YY1; BAP1 and YY1 are co-enriched at DR4/DR5 promoters by ChIP, and catalytic BAP1 mutant cannot repress DR4/DR5 promoter activity. Co-IP (BAP1-YY1), ChIP at DR4/DR5 promoters, reporter assays with WT and catalytic BAP1 mutant, YY1 siRNA knockdown, tissue microarrays The Journal of Biological Chemistry High 34597666
2022 Transportin-1 (TNPO1/Karyopherin β2) targets an atypical C-terminal proline-tyrosine nuclear localization signal (PY-NLS) on BAP1 and serves as its primary nuclear transporter; TNPO1 binding dissociates dimeric BAP1 and sequesters monoubiquitination sites flanking the PY-NLS to counteract UBE2O-mediated cytoplasmic retention of BAP1. Biochemical binding assays, nuclear import assays, domain mutagenesis (PY-NLS), BAP1 dimerization analysis, UBE2O competition assay The Journal of Cell Biology High 35446349
2023 Cryo-EM structure of human BAP1 with the ASXL1 DEUBAD domain bound to a H2AK119Ub nucleosome reveals molecular interactions of BAP1 and ASXL1 with histones and DNA that restructure the nucleosome and establish specificity for H2AK119Ub; >50 cancer-associated mutations in BAP1 and ASXL1 are mapped to mechanistically explain dysregulation of H2AK119Ub deubiquitination. Cryo-EM structure determination, biochemical reconstitution, cancer mutation structure-function analysis, cellular deubiquitination assays Science Advances High 37556531
2023 In osteoclasts, BAP1 deubiquitinase activity regulates osteoclast function through metabolic reprogramming: BAP1 deficiency elevates H2Aub at the SLC7A11 promoter and upregulates SLC7A11 expression, redirecting mitochondrial metabolites from the TCA cycle and altering ROS levels, thereby arresting osteoclast cytoskeletal organization and bone resorption. Bap1 conditional KO in myeloid cells (LysM-Cre), cytoskeletal organization assays, H2Aub ChIP at SLC7A11 promoter, metabolic profiling Nature Communications High 37740028
2015 BAP1 deubiquitinates and stabilizes MCRS1 (a centrosome component involved in spindle assembly), contributing to chromosome stability in renal cell carcinoma; BAP1 loss reduces MCRS1 levels and induces chromosomal instability. Co-IP, in vitro deubiquitination assay, chromosome stability assays, correlation in ccRCC tissue samples Cancer Letters Medium 26300492
2020 BAP1 deubiquitinates and stabilizes DIDO1 (a centrosome component required for spindle assembly) through deubiquitination, thereby maintaining chromosome stability in renal cell carcinoma. Co-IP, in vitro deubiquitination assay, chromosome stability assays, correlation in ccRCC tissues American Journal of Cancer Research Medium 32509391
2020 ASXL3 physically interacts with BRD4's extra-terminal (ET) domain via a novel BRD4-binding motif (BBM) and bridges BRD4 to the BAP1 complex; ASXL3 maintains chromatin occupancy of BRD4 at active enhancers in SCLC, and ASXL3 depletion causes genome-wide reduction of H3K27Ac and BRD4-dependent gene expression. Size exclusion chromatography, mass spectrometry, Co-IP, ChIP-seq (BRD4, H3K27Ac), RNA-seq, ASXL3 KO in SCLC cells Genome Medicine High 32669118
2020 C-terminally truncated ASXL1 loss of FOXK1/K2 interaction impairs the BAP1-ASXL1-FOXK1/K2 transcriptional network; wild-type ASXL1 interacts with FOXK1/K2 to regulate glucose metabolism, oxygen sensing, and JAK-STAT3 signaling pathway target genes via BAP1, and mutant ASXL1 dominantly inhibits this network. Co-IP (ASXL1-FOXK1/K2-BAP1), selective deletion of mutant allele, RNA-seq, gene expression rescue Protein & Cell Medium 32683582
2024 BAP1 deubiquitinates MAFF transcription factor (removing K48-linked ubiquitin) and stabilizes it; stabilized MAFF upregulates DUSP5 expression, which inhibits ERK phosphorylation and suppresses colorectal cancer growth. DUB screening library, Co-IP, in vitro deubiquitination assay, MAFF knockdown/overexpression, ERK pathway readouts, xenograft models European Journal of Cancer Medium 39151323
2024 BAP1 protects against disulfidptosis by suppressing SLC7A11-mediated cystine uptake (via H2Aub deubiquitination at SLC7A11 promoter) and by maintaining NADPH levels; loss of BAP1 or overexpression of SLC7A11 promotes disulfidptosis under glucose starvation. Cell death inhibitor profiling, disulfide bond accumulation assays, SLC7A11 KO/overexpression, erastin treatment, NADP+/NADPH measurement Oncogenesis Medium 39266549
2021 BAP1 overexpression enhances P53 activity and stability by reducing proteasome-mediated P53 degradation; the transcription factor ATF2 regulates BAP1 expression by binding the BAP1 promoter, placing BAP1 in an ATF2-BAP1-P53 axis mediating neuronal apoptosis. Luciferase assay (ATF2 binding to BAP1 promoter), Co-IP, P53 ubiquitination/stability assays, BAP1 shRNA knockdown in mouse SAH model Stroke Medium 38965653

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Frequent mutation of BAP1 in metastasizing uveal melanomas. Science (New York, N.Y.) 1150 21051595
2018 BAP1 links metabolic regulation of ferroptosis to tumour suppression. Nature cell biology 830 30202049
2012 BAP1 loss defines a new class of renal cell carcinoma. Nature genetics 768 22683710
2011 Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers. Journal of medical genetics 362 21941004
2017 BAP1 regulates IP3R3-mediated Ca2+ flux to mitochondria suppressing cell transformation. Nature 330 28614305
2013 Tumor suppressor and deubiquitinase BAP1 promotes DNA double-strand break repair. Proceedings of the National Academy of Sciences of the United States of America 305 24347639
2015 Loss of BAP1 function leads to EZH2-dependent transformation. Nature medicine 297 26437366
2012 BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs. Journal of translational medicine 239 22935333
2020 Biological Mechanisms and Clinical Significance of BAP1 Mutations in Human Cancer. Cancer discovery 231 32690542
2009 The deubiquitinating enzyme BAP1 regulates cell growth via interaction with HCF-1. The Journal of biological chemistry 223 19815555
2013 Tumours associated with BAP1 mutations. Pathology 222 23277170
2013 Germline BAP1 mutations predispose to renal cell carcinomas. American journal of human genetics 220 23684012
2018 Comprehensive Study of the Clinical Phenotype of Germline BAP1 Variant-Carrying Families Worldwide. Journal of the National Cancer Institute 203 30517737
2015 BAP1 promotes breast cancer cell proliferation and metastasis by deubiquitinating KLF5. Nature communications 179 26419610
2016 BAP1/ASXL1 recruitment and activation for H2A deubiquitination. Nature communications 165 26739236
2017 Germline and somatic BAP1 mutations in high-grade rhabdoid meningiomas. Neuro-oncology 152 28170043
2017 Modeling Renal Cell Carcinoma in Mice: Bap1 and Pbrm1 Inactivation Drive Tumor Grade. Cancer discovery 144 28473526
2020 BAP1: Not just a BRCA1-associated protein. Cancer treatment reviews 139 32877777
2021 Roles and mechanisms of BAP1 deubiquitinase in tumor suppression. Cell death and differentiation 134 33462414
2014 Germline mutation of Bap1 accelerates development of asbestos-induced malignant mesothelioma. Cancer research 115 24928783
2015 The BAP1/ASXL2 Histone H2A Deubiquitinase Complex Regulates Cell Proliferation and Is Disrupted in Cancer. The Journal of biological chemistry 113 26416890
2018 Mutant ASXL1 cooperates with BAP1 to promote myeloid leukaemogenesis. Nature communications 109 30013160
2015 Loss of expression of BAP1 predicts longer survival in mesothelioma. Pathology 103 25938359
2014 Stabilization and targeting of INO80 to replication forks by BAP1 during normal DNA synthesis. Nature communications 103 25283999
2011 An emerging model for BAP1's role in regulating cell cycle progression. Cell biochemistry and biophysics 102 21484256
2013 PBRM1 and BAP1 as novel targets for renal cell carcinoma. Cancer journal (Sudbury, Mass.) 98 23867514
2007 The Arabidopsis BAP1 and BAP2 genes are general inhibitors of programmed cell death. Plant physiology 94 17631528
2017 Genotypic and Phenotypic Features of BAP1 Cancer Syndrome: A Report of 8 New Families and Review of Cases in the Literature. JAMA dermatology 88 28793149
2017 SF3B1 and BAP1 mutations in blue nevus-like melanoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 85 28409567
2014 Germline BAP1 mutations predispose also to multiple basal cell carcinomas. Clinical genetics 83 25080371
2017 BAP1 inhibits the ER stress gene regulatory network and modulates metabolic stress response. Proceedings of the National Academy of Sciences of the United States of America 82 28275095
2018 Overview of BAP1 cancer predisposition syndrome and the relationship to uveal melanoma. Journal of current ophthalmology 81 29988936
2016 BAP1 Immunohistochemistry and p16 FISH in the Diagnosis of Sarcomatous and Desmoplastic Mesotheliomas. The American journal of surgical pathology 81 26900815
2016 Gene of the month: BAP1. Journal of clinical pathology 76 27235536
2014 BRCA1-associated protein 1 (BAP1) deubiquitinase antagonizes the ubiquitin-mediated activation of FoxK2 target genes. The Journal of biological chemistry 74 25451922
2012 The ASXL-BAP1 axis: new factors in myelopoiesis, cancer and epigenetics. Leukemia 72 23147254
2017 BAP1 dependent expression of long non-coding RNA NEAT-1 contributes to sensitivity to gemcitabine in cholangiocarcinoma. Molecular cancer 71 28122578
2021 Epigenetic targeted therapy of stabilized BAP1 in ASXL1 gain-of-function mutated leukemia. Nature cancer 68 35122023
2017 Diagnostic utility of BAP1 and EZH2 expression in malignant mesothelioma. Histopathology 67 27859460
2016 CDKN2A and BAP1 germline mutations predispose to melanoma and mesothelioma. Cancer letters 61 27181379
2017 BAP1, a tumor suppressor gene driving malignant mesothelioma. Translational lung cancer research 56 28713672
2019 BRCA1-associated protein (BAP1)-inactivated melanocytic tumors. Journal of cutaneous pathology 53 31233225
2020 ASXL3 bridges BRD4 to BAP1 complex and governs enhancer activity in small cell lung cancer. Genome medicine 51 32669118
2022 Clinical and molecular validation of BAP1, MTAP, P53, and Merlin immunohistochemistry in diagnosis of pleural mesothelioma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 50 35459788
2016 Loss of BAP1 Expression Occurs Frequently in Intrahepatic Cholangiocarcinoma. Medicine 50 26765459
2019 BAP1 Loss Is Associated with DNA Methylomic Repatterning in Highly Aggressive Class 2 Uveal Melanomas. Clinical cancer research : an official journal of the American Association for Cancer Research 49 31285370
2013 A BAP1 mutation in a Danish family predisposes to uveal melanoma and other cancers. PloS one 47 23977234
2021 BAP1-Mutated Clear Cell Renal Cell Carcinoma. American journal of clinical pathology 46 33210135
2020 Combined deletion of Bap1, Nf2, and Cdkn2ab causes rapid onset of malignant mesothelioma in mice. The Journal of experimental medicine 46 32271879
2021 Roles of the BAP1 Tumor Suppressor in Cell Metabolism. Cancer research 45 33446574
2021 Estimation of the timing of BAP1 mutation in uveal melanoma progression. Scientific reports 45 33903674
2023 Structural basis of histone H2A lysine 119 deubiquitination by Polycomb repressive deubiquitinase BAP1/ASXL1. Science advances 41 37556531
2023 Clinical practice guidelines for the diagnosis and surveillance of BAP1 tumour predisposition syndrome. European journal of human genetics : EJHG 41 37607989
2020 BAP1: role in carcinogenesis and clinical implications. Translational lung cancer research 40 32206571
2021 BAP1/ASXL complex modulation regulates epithelial-mesenchymal transition during trophoblast differentiation and invasion. eLife 39 34170818
2015 Stabilization of MCRS1 by BAP1 prevents chromosome instability in renal cell carcinoma. Cancer letters 39 26300492
2020 Identifying BAP1 Mutations in Clear-Cell Renal Cell Carcinoma by CT Radiomics: Preliminary Findings. Frontiers in oncology 36 32185138
2016 BAP1 suppresses lung cancer progression and is inhibited by miR-31. Oncotarget 36 26885612
2020 BAP1 suppresses prostate cancer progression by deubiquitinating and stabilizing PTEN. Molecular oncology 35 33155366
2017 A population-based analysis of germline BAP1 mutations in melanoma. Human molecular genetics 34 28062663
2016 Loss of expression of BAP1 is very rare in non-small cell lung carcinoma. Pathology 33 27114369
2015 Analysis of BAP1 Germline Gene Mutation in Young Uveal Melanoma Patients. Ophthalmic genetics 32 25687217
2020 CCR5 blockade inflames antitumor immunity in BAP1-mutant clear cell renal cell carcinoma. Journal for immunotherapy of cancer 31 32371459
2018 BAP1 regulation of the key adaptor protein NCoR1 is critical for γ-globin gene repression. Genes & development 31 30463901
2022 The expanding role of BAP1 in clear cell renal cell carcinoma. Human pathology 29 35932824
2020 Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network. Protein & cell 29 32683582
2021 BAP1 forms a trimer with HMGB1 and HDAC1 that modulates gene × environment interaction with asbestos. Proceedings of the National Academy of Sciences of the United States of America 28 34815344
2019 BAP1 promotes stalled fork restart and cell survival via INO80 in response to replication stress. The Biochemical journal 28 31657441
2020 The Tumor Suppressor BAP1 Regulates the Hippo Pathway in Pancreatic Ductal Adenocarcinoma. Cancer research 27 31988076
2023 BAP1 promotes osteoclast function by metabolic reprogramming. Nature communications 24 37740028
2021 BAP1 antagonizes WWP1-mediated transcription factor KLF5 ubiquitination and inhibits autophagy to promote melanoma progression. Experimental cell research 24 33516665
2015 A novel BAP1 mutation is associated with melanocytic neoplasms and thyroid cancer. Cancer genetics 23 26774355
2021 Co-occurrence of BAP1 and SF3B1 mutations in uveal melanoma induces cellular senescence. Molecular oncology 22 34706158
2020 Uveal Melanoma in BAP1 Tumor Predisposition Syndrome: Estimation of Risk. American journal of ophthalmology 21 33316260
2019 Population-based analysis of BAP1 germline variations in patients with uveal melanoma. Human molecular genetics 21 31058963
2022 Multi-omics Profiling Shows BAP1 Loss Is Associated with Upregulated Cell Adhesion Molecules in Uveal Melanoma. Molecular cancer research : MCR 20 35426938
2021 Novel insights into the BAP1-inactivated melanocytic tumor. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 20 34857909
2018 The diagnostic role of BAP1 in serous effusions. Human pathology 20 29802871
2022 LncRNA NEAT1 promoted MPP+‑induced ferroptosis via regulating miR‑150‑5p/BAP1 pathway in SK‑N‑SH cells. Acta neurobiologiae experimentalis 19 35833822
2019 BAP1 in solid tumors. Future oncology (London, England) 19 31159579
2024 Tumor suppressor BAP1 suppresses disulfidptosis through the regulation of SLC7A11 and NADPH levels. Oncogenesis 17 39266549
2023 Genetic screens reveal new targetable vulnerabilities in BAP1-deficient mesothelioma. Cell reports. Medicine 17 36657447
2023 ITGB2-ICAM1 axis promotes liver metastasis in BAP1-mutated uveal melanoma with retained hypoxia and ECM signatures. Cellular oncology (Dordrecht, Netherlands) 17 38150154
2018 G-quadruplexes in the BAP1 promoter positively regulate its expression. Experimental cell research 17 29787736
2022 Intrinsic Disorder in BAP1 and Its Association with Uveal Melanoma. Genes 16 36292588
2022 BAP1 in cancer: epigenetic stability and genome integrity. Discover oncology 16 36318367
2020 Glutamylation of deubiquitinase BAP1 controls self-renewal of hematopoietic stem cells and hematopoiesis. The Journal of experimental medicine 16 31699823
2021 Intratumor Heterogeneity in Uveal Melanoma BAP-1 Expression. Cancers 15 33800007
2021 The AMP-dependent kinase pathway is upregulated in BAP1 mutant uveal melanoma. Pigment cell & melanoma research 15 34347929
2020 BAP1 maintains chromosome stability by stabilizing DIDO1 in renal cell carcinoma. American journal of cancer research 15 32509391
2022 Pyruvate dehydrogenase inactivation causes glycolytic phenotype in BAP1 mutant uveal melanoma. Oncogene 14 35046531
2022 Impacts of Cancer-associated Mutations on the Structure-Activity Relationship of BAP1. Journal of molecular biology 14 35317997
2021 BAP1 promotes viability and migration of ECA109 cells through KLF5/CyclinD1/FGF-BP1. FEBS open bio 14 33529461
2021 The spectrum of tumors harboring BAP1 gene alterations. Cancer genetics 14 33866194
2022 Tumor suppressor BAP1 nuclear import is governed by transportin-1. The Journal of cell biology 13 35446349
2021 Regulation of B Lymphocyte Development by Histone H2A Deubiquitinase BAP1. Frontiers in immunology 13 33912157
2024 ATF2/BAP1 Axis Mediates Neuronal Apoptosis After Subarachnoid Hemorrhage via P53 Pathway. Stroke 12 38965653
2024 BAP1-mediated MAFF deubiquitylation regulates tumor growth and is associated with adverse outcomes in colorectal cancer. European journal of cancer (Oxford, England : 1990) 12 39151323
2022 BAP1 loss induces mitotic defects in mesothelioma cells through BRCA1-dependent and independent mechanisms. Oncogene 12 36550359
2021 BAP1 and YY1 regulate expression of death receptors in malignant pleural mesothelioma. The Journal of biological chemistry 12 34597666