Affinage

BAP1

Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1 · UniProt Q96QZ7

Length
1491 aa
Mass
164.6 kDa
Annotated
2026-06-09
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BAP1 is a UCH-family deubiquitinase that operates principally on chromatin to oppose Polycomb-mediated silencing, while also stabilizing a wide range of non-histone substrates to control cell proliferation, metabolic stress responses, and programmed cell death (PMID:26739236, PMID:30664650). As the catalytic subunit of the PR-DUB/BAP1 core complex, its C-terminal extension auto-recruits it to nucleosomes and is allosterically activated by the DEUBAD domains of ASXL1/2/3 to specifically remove monoubiquitin from H2AK119, a reaction it cannot perform on DNA-damage-dependent H2A K13/K15 ubiquitination (PMID:26739236); a cryo-EM structure of the BAP1–ASXL1 DEUBAD complex on a H2AK119Ub nucleosome explains how the enzyme restructures the nucleosome to achieve this specificity and rationalizes >50 cancer-associated mutations (PMID:37556531). Rather than driving repression, the assembled BAP1 complex safeguards transcriptionally active genes against PRC1-mediated silencing (PMID:30664650), with complex chromatin occupancy stabilized by MBD5/MBD6 binding to ASXL PHD fingers and bridged to active enhancers via an ASXL3–BRD4 interaction (PMID:36180891, PMID:32669118). Through H2Aub regulation at the SLC7A11 promoter, BAP1 represses the cystine transporter to elevate lipid peroxidation and promote ferroptosis as a tumor-suppressor output (PMID:30202049, PMID:30907299). Beyond chromatin, BAP1 deubiquitinates and stabilizes numerous substrates including HCF-1, KLF5, PTEN, LATS, HIF-1α, and SMN, coupling its activity to cell-cycle control, Hippo and AKT signaling, hypoxic adaptation, and tissue maintenance (PMID:19815555, PMID:26419610, PMID:33155366, PMID:31988076, PMID:36656861, PMID:35603786). It localizes to the ER to deubiquitinate and stabilize IP3R3, sustaining Ca2+ flux that promotes apoptosis (PMID:28614305), and is required at DNA double-strand breaks, where catalytic activity and IR-induced phosphorylation drive its recruitment to facilitate BRCA1/RAD51-dependent homologous recombination (PMID:24347639). Its predominantly nuclear function depends on Transportin-1 recognition of an atypical C-terminal PY-NLS that counteracts UBE2O-mediated cytosolic retention (PMID:35446349).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2009 High

    Establishing BAP1 as a deubiquitinase with a defined substrate addressed whether its growth-regulatory role was enzymatic, identifying HCF-1 as the first physiological substrate.

    Evidence MS co-purification, Co-IP, ubiquitin chain-linkage analysis, and HBM-mutant rescue

    PMID:19815555

    Open questions at the time
    • Did not define the chromatin/histone substrate
    • Mechanism of growth regulation downstream of HCF-1 unresolved
  2. 2013 High

    Linking BAP1 to DNA repair answered whether it acts in genome maintenance, showing both catalysis and IR-induced phosphorylation are needed for recruitment to double-strand breaks and homologous recombination.

    Evidence DT40 knockout, IR sensitivity, BRCA1/RAD51 foci imaging, I-SceI DSB assay, phosphomutant analysis

    PMID:24347639

    Open questions at the time
    • Relevant deubiquitination substrate at DSBs not identified
    • Kinase responsible for IR-induced phosphorylation unknown
  3. 2015 High

    Multiple studies expanded the non-histone substrate repertoire and connected BAP1 loss to Polycomb mark dysregulation, defining how it controls proliferation and chromosome stability.

    Evidence Conditional Bap1 KO mice with ChIP-seq and epistasis; genome-wide DUB screens with Co-IP, deubiquitination assays, and xenograft rescue (KLF5, MCRS1)

    PMID:26300492 PMID:26419610 PMID:26437366

    Open questions at the time
    • Direct vs indirect effects on H3K27me3/EZH2 not fully separated
    • Whether substrate stabilization is cell-type specific unclear
  4. 2016 High

    Biochemical reconstitution defined the catalytic mechanism, showing BAP1's C-terminal extension auto-recruits it to nucleosomes and ASXL DEUBAD domains activate H2AK119-specific deubiquitination.

    Evidence In vitro reconstitution with purified nucleosomes, C-terminal mutagenesis, and substrate specificity assays (H2AK119 vs K13/15)

    PMID:26739236

    Open questions at the time
    • Atomic basis of specificity not yet resolved
    • Role of complex on native chromatin not addressed in vitro
  5. 2017 Medium

    Identifying ER-localized IP3R3 deubiquitination and ER-stress transcriptional repression broadened BAP1 beyond the nucleus, linking it to Ca2+-driven apoptosis and UPR control.

    Evidence Subcellular fractionation, Co-IP, deubiquitylation and Ca2+ flux assays; ChIP at ATF3/CHOP promoters in Bap1 KO mice

    PMID:28275095 PMID:28614305

    Open questions at the time
    • How BAP1 partitions between ER and nucleus unresolved
    • ER targeting determinants not mapped
  6. 2018 Medium

    Work on the SLC7A11/ferroptosis axis and additional complex interactions established a metabolic tumor-suppressor output and refined the complex's repertoire (HMGB1/HDAC1, DRED, ASXL1-MT leukemia).

    Evidence ChIP, deubiquitinase-dead mutants, cystine uptake and lipid peroxidation assays, in vivo tumor models; Co-IP and ubiquitylation assays

    PMID:30013160 PMID:30202049 PMID:30463901 PMID:34815344

    Open questions at the time
    • Direct vs indirect H2Aub effects on SLC7A11 not fully separated
    • Tissue-specificity of complex composition unclear
  7. 2019 High

    Reframing the BAP1 complex as a transcriptional activator overturned its presumed silencing role, showing it safeguards active genes against PRC1, and clarified SLC7A11 regulation requires dynamic H2Aub.

    Evidence Isogenic CRISPR lines with ChIP-seq/RNA-seq and catalytic-mutant complementation; H2Aub ChIP with NRF2/ATF4 knockdown

    PMID:30664650 PMID:30907299 PMID:31657441

    Open questions at the time
    • How dynamic H2Aub turnover is coordinated with PRC1 unresolved
    • Genome-wide rules for activation vs repression unclear
  8. 2021 Medium

    A series of studies defined further stabilized substrates (PTEN, LATS, HIF-1α, INO80) and physiological roles in B-cell development and mesothelioma ROS homeostasis, mapping BAP1 onto major signaling and stress pathways.

    Evidence Co-IP, deubiquitination assays with mutagenesis, conditional KO mice, proteomics, and fork/restart assays

    PMID:29069806 PMID:31988076 PMID:33155366 PMID:33658435 PMID:33912157 PMID:34597666 PMID:36656861

    Open questions at the time
    • Many substrate interactions rest on single-lab Co-IP
    • Direct vs indirect contributions to each pathway not always separated
  9. 2022 Medium

    Defining the PY-NLS/Transportin-1 import mechanism and chromatin-stabilizing MBD5/6 interactions explained how BAP1 reaches and persists on its nuclear targets, while HDX-MS clarified non-catalytic cancer mutations.

    Evidence Co-IP, nuclear import assays, NLS/dimerization mutagenesis; complex purification with ChIP-seq; HDX-MS on UCH-domain mutants

    PMID:35317997 PMID:35446349 PMID:36180891

    Open questions at the time
    • Regulation of UBE2O-driven cytosolic retention in vivo unclear
    • Functional consequence of aggregation-prone mutants in cells not fully tested
  10. 2023 High

    The cryo-EM structure of BAP1–ASXL1 on a H2AK119Ub nucleosome provided the atomic basis for substrate specificity and rationalized cancer mutations, completing the mechanistic picture of the chromatin reaction.

    Evidence Cryo-EM structure with biochemical deubiquitination, structure-guided mutagenesis, and cellular validation

    PMID:37556531

    Open questions at the time
    • Structures with ASXL2/ASXL3 not determined
    • Dynamics of nucleosome restructuring not captured
  11. 2025 Medium

    Recent work added regulatory feedback (FOXO3a) and disease-context outputs (disulfidptosis, neuronal ferroptosis/apoptosis), but a unified model integrating chromatin, substrate, and feedback layers is still incomplete.

    Evidence Co-IP, deubiquitination assays, promoter reporters, ChIP, and in vivo models

    PMID:39151323 PMID:39266549 PMID:40080966

    Open questions at the time
    • Hierarchy among the many proposed substrates/outputs unresolved
    • Context-dependence of pro- vs anti-death roles unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single deubiquitinase coordinately selects among its chromatin and dozens of non-histone substrates in a tissue- and context-specific manner, and how this dictates its tumor-suppressor versus cell-death outputs, remains unresolved.
  • No quantitative substrate hierarchy
  • Determinants of cytoplasmic vs nuclear vs ER function not integrated
  • In vivo relevance of many single-lab substrates untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0098772 molecular function regulator activity 4 GO:0140110 transcription regulator activity 4 GO:0016787 hydrolase activity 3 GO:0042393 histone binding 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-4839726 Chromatin organization 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-73894 DNA Repair 2
Partners
ASXL1ASXL2ASXL3BRD4HCF-1INO80IP3R3MBD6
Complex memberships
BAP1/HCF-1 complexDRED repressor complexPR-DUB / BAP1 core complex (BAP1-ASXL1/2/3)

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 BAP1 represses SLC7A11 (cystine transporter) expression by reducing histone H2A ubiquitination (H2Aub) on the SLC7A11 promoter in a deubiquitinating-dependent manner, thereby inhibiting cystine uptake, elevating lipid peroxidation, and promoting ferroptosis as a tumor suppressor mechanism. Integrated transcriptomic/epigenomic analyses, ChIP assays, functional deubiquitinase-dead mutants, cystine uptake assays, lipid peroxidation measurements, and in vivo tumor models Nature cell biology High 30202049
2017 BAP1 localizes at the endoplasmic reticulum where it binds, deubiquitylates, and stabilizes the type 3 inositol-1,4,5-trisphosphate receptor (IP3R3), thereby modulating calcium (Ca2+) release from the ER into the cytosol and mitochondria to promote apoptosis. Subcellular fractionation, co-immunoprecipitation, deubiquitylation assays, Ca2+ flux measurements, cellular transformation assays, and genetic models (BAP1+/- cells) Nature High 28614305
2013 BAP1 is required for efficient assembly of homologous recombination (HR) factors BRCA1 and RAD51 at ionizing radiation-induced foci; BAP1-deficient cells are sensitive to DSB-inducing agents, defective in HR-mediated gene conversion, and exhibit increased chromosomal breaks. Both catalytic activity and IR-induced phosphorylation of BAP1 are required for its recruitment to DSB sites and for DNA repair. RNAi screen, gene knockout in DT40 cells, IR sensitivity assays, immunofluorescence for BRCA1/RAD51 foci, I-SceI-induced DSB assay, phosphomutant analysis Proceedings of the National Academy of Sciences of the United States of America High 24347639
2009 BAP1 interacts with host cell factor-1 (HCF-1) via an HCF-1 binding motif (HBM); HCF-1N is modified with Lys-48-linked polyubiquitin chains on its Kelch domain, and BAP1 deubiquitinates HCF-1N. This interaction is required for BAP1-mediated cell growth regulation. Mass spectrometry co-purification, co-immunoprecipitation, ubiquitin chain-linkage analysis, RNAi depletion, dominant-negative mutant overexpression The Journal of biological chemistry High 19815555
2015 BAP1 loss in mice results in increased H3K27me3 levels, elevated EZH2 expression, and enhanced PRC2-target repression; this is mechanistically linked to a marked decrease in H4K20 monomethylation (H4K20me1), and SETD8 (the H4K20me1 methyltransferase) overexpression reduces EZH2 expression and abrogates BAP1-mutant cell proliferation. Conditional Bap1 knockout mice, ChIP-seq for histone marks, epistasis via Bap1/Ezh2 double conditional deletion, SETD8 overexpression rescue experiments Nature medicine High 26437366
2016 BAP1's C-terminal extension auto-recruits BAP1 to nucleosomes (in an acidic patch-independent manner), forming an unproductive initial complex that is activated by the DEUBAD domains of ASXL1, ASXL2, or ASXL3 to increase BAP1's affinity for ubiquitin on H2A and drive deubiquitination. The reaction is specific for Polycomb H2AK119 modifications and cannot deubiquitinate DNA damage-dependent H2A K13/K15 ubiquitination. Biochemical reconstitution with purified nucleosomes, mutagenesis of BAP1 C-terminal extension, DEUBAD domain binding assays, specificity assays comparing H2AK119 vs H2AK13/15 substrates Nature communications High 26739236
2023 Cryo-EM structure of human BAP1 and the ASXL1 DEUBAD domain in complex with a H2AK119Ub nucleosome reveals the molecular interactions of BAP1 and ASXL1 with histones and DNA that restructure the nucleosome to establish specificity for H2AK119Ub; >50 cancer-associated mutations in BAP1 and ASXL1 are structurally explained as dysregulating this reaction. Cryo-EM structure determination, biochemical deubiquitination assays, mutagenesis of contact residues, cellular validation Science advances High 37556531
2019 BAP1-associated core complex (BAP1.com), containing ASXL1/2/3, functions as a transcriptional activator to safeguard transcriptionally active genes against silencing by Polycomb Repressive Complex 1 (PRC1), rather than participating in Polycomb-mediated silencing as previously proposed. CRISPR/Cas9-generated isogenic cell lines, integrative ChIP-seq/RNA-seq, catalytic mutant BAP1 complementation, H2AK119Ub profiling Nature communications High 30664650
2015 BAP1 acts as a deubiquitinase for KLF5; BAP1 directly interacts with KLF5 and stabilizes it via deubiquitination. KLF5 is a component of the BAP1/HCF-1 complex, which promotes cell cycle progression partly by inhibiting p27 gene expression. BAP1 knockdown inhibits tumorigenicity and lung metastasis, partially rescued by ectopic KLF5 expression. Genome-wide siRNA DUB screen, co-immunoprecipitation, in vitro deubiquitination assay, ubiquitination assay, rescue experiments, xenograft tumor models Nature communications High 26419610
2018 BAP1 forms a trimeric protein complex with HMGB1 and histone deacetylase 1 (HDAC1) that modulates HMGB1 acetylation and secretion; reduced BAP1 levels cause increased ubiquitylation and degradation of HDAC1, leading to increased HMGB1 acetylation and its active secretion, promoting mesothelial cell transformation. Co-immunoprecipitation, ubiquitylation assays, serum HMGB1 acetylation measurements (ELISA), cellular transformation assays in BAP1+/- cells Proceedings of the National Academy of Sciences of the United States of America High 34815344
2018 BAP1 is a component of the DRED repressor complex in erythroid cells; it maintains NCoR1 occupancy at the β-globin locus, and BAP1 inhibition massively induces γ-globin synthesis, demonstrating a role in γ-globin gene repression. Co-immunoprecipitation, ChIP assays at β-globin locus, BAP1 inhibition in erythroid cells with γ-globin expression readout Genes & development Medium 30463901
2019 BAP1 promotes restart of hydroxyurea-induced stalled replication forks by recruiting the INO80 chromatin remodeler to stalled forks; BAP1 depletion abrogates INO80 binding at replication forks, increases RAD51 foci, and causes hypersensitivity to HU, rescued by INO80 re-expression. DNA fiber assays (fork restart), ChIP at replication forks, immunofluorescence, HU sensitivity assays, ectopic INO80 rescue The Biochemical journal Medium 31657441
2021 CHIP (E3 ubiquitin ligase) polyubiquitinates INO80 in an Hsp70-dependent manner; BAP1 and CHIP act in concert to stabilize INO80 and promote its chromatin binding, which is required for efficient replication fork progression. Co-immunoprecipitation, ubiquitination assays, half-life (cycloheximide chase) experiments, DNA fiber assays, ChIP Molecules and cells Medium 33658435
2018 BAP1 induces cell death via interaction with 14-3-3 protein; the BAP1-14-3-3 association releases the apoptotic inducer Bax from 14-3-3, promoting cell death through the intrinsic apoptosis pathway. Co-immunoprecipitation, Bax release assay, apoptosis assays, cell cycle analysis, xenograft tumor models Cell death & disease Medium 29686263
2015 BAP1 binds to MCRS1 (a centrosome/spindle assembly component) and stabilizes it via deubiquitination, contributing to chromosome stability in renal cell carcinoma. Co-immunoprecipitation, deubiquitination assay, chromosome stability assays, expression correlation in ccRCC tissues Cancer letters Medium 26300492
2020 BAP1 physically binds and deubiquitinates PTEN, inhibiting ubiquitination-mediated PTEN degradation and thereby stabilizing PTEN protein; this suppresses the AKT signaling pathway and prostate cancer progression, which is reversed by BAP1 knockdown and rescued by PTEN re-expression. Co-immunoprecipitation, deubiquitination assay, knockdown/overexpression in PCa cells, AKT signaling measurements, PTEN re-expression rescue, xenograft models Molecular oncology Medium 33155366
2020 BAP1 stabilizes the LATS tumor suppressor kinase (Hippo pathway) by preventing its ubiquitin-dependent proteasomal degradation; BAP1-deficient pancreatic tumors show enhanced LATS degradation and Hippo pathway deregulation. Conditional Bap1 KO mouse model (KrasG12D background), ubiquitination/proteasome assays for LATS, histological and pathway analysis of pancreatic tumors Cancer research Medium 31988076
2021 BAP1 binds, deubiquitylates, and stabilizes HIF-1α during hypoxia; BAP1 interacts with the N-terminal region of HIF-1α where HIF-1α binds DNA and dimerizes with HIF-1β. BAP1 residues I675, F678, I679, and L691 in the C-terminal domain-NLS are required for HIF-1α interaction. Loss of BAP1 reduces nuclear HIF-1α levels in hypoxic cells. Co-immunoprecipitation, deubiquitylation assays, site-directed mutagenesis of BAP1 C-terminal residues, computational docking, immunofluorescence/IHC in BAP1-null cells and mesothelioma biopsies Proceedings of the National Academy of Sciences of the United States of America Medium 36656861
2022 Transportin-1 (TNPO1/Karyopherin β2) is the primary nuclear transporter of BAP1, targeting an atypical C-terminal proline-tyrosine nuclear localization signal (PY-NLS). TNPO1 binding dissociates dimeric BAP1 and sequesters monoubiquitination sites flanking the PY-NLS, counteracting UBE2O-mediated cytosolic retention of BAP1. Co-immunoprecipitation, nuclear import assays, PY-NLS mutagenesis, BAP1 dimerization analysis, UBE2O competition assays The Journal of cell biology Medium 35446349
2018 Mutant ASXL1 (C-terminally truncated) undergoes increased monoubiquitination, which in turn increases the catalytic function of BAP1; the hyperactive ASXL1-MT/BAP1 complex promotes aberrant myeloid differentiation and leukaemogenesis by removing H2AK119 ubiquitination at posterior HOXA genes and IRF8 loci. Biochemical ubiquitination assays, deubiquitinase activity assays of BAP1/ASXL1-MT complex, ChIP for H2AK119ub, haematopoietic progenitor differentiation assays, BAP1 depletion in ASXL1-MT leukemia cells Nature communications Medium 30013160
2021 BAP1 downregulation is essential to trigger epithelial-mesenchymal transition (EMT) during trophoblast differentiation; BAP1's function in suppressing EMT is dependent on its binding to ASXL1/2 proteins to form the PR-DUB complex. CRISPR KO of BAP1 in mouse trophoblast stem cells increases invasiveness, and this is conserved in human trophoblast stem cells. CRISPR/Cas9 KO and overexpression in mouse and human trophoblast stem cells, EMT marker analysis, invasion assays, BAP1-ASXL interaction requirement tested by mutant complementation eLife Medium 34170818
2017 BAP1 inhibits cell death induced by metabolic stress (ER stress/UPR) in a deubiquitinating activity-dependent manner by repressing ATF3 and CHOP transcription; BAP1 binds to ATF3 and CHOP promoters and inhibits their transcription. Bap1 KO mice are more sensitive to tunicamycin-induced renal damage. BAP1 KO mouse (tunicamycin model), ChIP at ATF3/CHOP promoters, ROS/ATP measurements, cell death assays with catalytic mutant BAP1 Proceedings of the National Academy of Sciences of the United States of America Medium 28275095
2021 BAP1 binds YY1 transcription factor and, together with YY1, occupies the promoter regions of TRAIL death receptors DR4 and DR5 to repress their transcription; catalytically inactive BAP1 fails to reduce DR4/DR5 promoter activity, indicating deubiquitinase activity is required. Co-immunoprecipitation of BAP1-YY1, ChIP at DR4/DR5 promoters, luciferase reporter assays with wt and catalytic mutant BAP1, BAP1 and YY1 knockdown with DR4/DR5 expression readout The Journal of biological chemistry Medium 34597666
2022 MBD5 and MBD6 bind to the C-terminal PHD fingers of ASXL1-3 scaffold proteins and stabilize the BAP1 complex at chromatin; depletion of MBD6 causes global loss of BAP1 chromatin occupancy and reduces BAP1-dependent gene expression and tumor growth in SCLC. Biochemical complex purification/size exclusion chromatography, mass spectrometry, ChIP-seq, RNA-seq, MBD6 depletion in SCLC cells and xenografts Genome biology Medium 36180891
2022 BAP1 stabilizes SMN (survival of motor neuron protein) in fibro-adipogenic progenitors (FAPs) expressing Dpp4 by preventing SMN's ubiquitination-dependent degradation; Bap1 deletion in these cells reduces SMN levels, causing neuromuscular junction degeneration and motor neuron loss, which is rescued by ubiquitination-resistant SMN (SMNK186R). Conditional Bap1 KO in Dpp4+ FAPs (mouse), ubiquitination assays, SMN protein stability assays, neuromuscular phenotype analysis, SMNK186R rescue, cell transplantation JCI insight Medium 35603786
2020 ASXL3 functions as an adaptor protein that directly interacts with BRD4's extra-terminal (ET) domain via a novel BRD4 binding motif (BBM), bridging the BAP1 complex to BRD4 at active enhancers in SCLC; depletion of ASXL3 reduces genome-wide H3K27Ac levels and BRD4-dependent gene expression. Size exclusion chromatography, mass spectrometry, co-immunoprecipitation, ChIP-seq, RNA-seq, ASXL3 depletion Genome medicine Medium 32669118
2020 Wild-type ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 as part of the BAP1-ASXL1 complex to regulate a subset of FOXK1/K2 target genes involved in glucose metabolism, oxygen sensing, and JAK-STAT3 signaling; C-terminally truncated mutant ASXL1 loses the ability to interact with FOXK1/K2 and dominantly inhibits the wild-type ASXL1-BAP1-TF interaction. Co-immunoprecipitation, ASXL1 mutant allele deletion, rescue experiments, gene expression analysis of FOXK1/K2 target genes Protein & cell Medium 32683582
2023 BAP1 promotes osteoclast function via metabolic reprogramming; BAP1 deubiquitinase activity controls SLC7A11 expression through H2Aub occupancy at its promoter, which regulates cellular ROS and redirects mitochondrial metabolites away from the TCA cycle, both necessary for osteoclast cytoskeletal organization and bone resorption. Myeloid-specific Bap1 KO mice, bone mass phenotyping, H2Aub ChIP at SLC7A11 promoter, SLC7A11 expression analysis, metabolic profiling Nature communications Medium 37740028
2020 BAP1 maintains chromosome stability by binding and stabilizing DIDO1 (a centrosome/spindle assembly component) through deubiquitination in renal cell carcinoma cells. Co-immunoprecipitation, deubiquitination assay, chromosome stability assays, expression correlation in ccRCC tissues American journal of cancer research Low 32509391
2024 BAP1 deubiquitinates MAFF (a bZIP transcription factor) to stabilize it against K48-linked ubiquitination-mediated proteasomal degradation; stabilized MAFF upregulates DUSP5, resulting in inhibition of ERK phosphorylation and suppression of colorectal cancer growth. DUB expression library screening, co-immunoprecipitation, deubiquitination assay, DUSP5 expression analysis, ERK phosphorylation measurements, in vitro and in vivo tumor growth assays European journal of cancer Medium 39151323
2024 BAP1 protects against disulfidptosis (a cell death mode caused by cystine accumulation and NADPH depletion) by repressing SLC7A11 expression via H2Aub regulation, reducing intracellular cystine uptake; overexpressing SLC7A11 or adding exogenous cystine counteracts BAP1's protective effect, and BAP1 loss also lowers NADPH levels. Cell death inhibitor profiling, disulfide bond accumulation assays, SLC7A11 KO and overexpression, cystine uptake assays, NADP+/NADPH measurements Oncogenesis Medium 39266549
2025 FOXO3a transcriptionally regulates BAP1 by binding to the BAP1 promoter; BAP1 in turn deubiquitinates FOXO3a (at K48 sites) via its UCH domain to stabilize FOXO3a. BAP1 overexpression increases SLC7A11 repression and GPX4 suppression via H2Aub, promoting neuronal ferroptosis after subarachnoid hemorrhage. Luciferase reporter assays, co-immunoprecipitation, deubiquitination assay, ChIP at SLC7A11 promoter, BAP1 overexpression/siRNA knockdown, mouse SAH model with lentiviral shBAP1 Redox biology Medium 40080966
2024 ATF2 transcription factor regulates BAP1 expression by binding to the BAP1 promoter; BAP1 enhances P53 stability by reducing its proteasome-mediated degradation, and elevated P53 promotes neuronal apoptosis via the P53 pathway after subarachnoid hemorrhage. Luciferase assay (ATF2 binding to BAP1 promoter), co-immunoprecipitation, P53 ubiquitination/stability assays, BAP1 shRNA in SAH mouse model Stroke Low 38965653
2019 SLC7A11 repression by BAP1 occurs independently of NRF2 and ATF4 transcription factors; both BAP1 (which decreases H2Aub) and PRC1 (a major H2Aub E3 ligase that increases H2Aub) repress SLC7A11 expression, suggesting dynamic regulation of H2Aub is required for SLC7A11 repression; BAP1 promotes ferroptosis induced by class I FIN (erastin) but not class II FIN (RSL3). H2Aub ChIP at SLC7A11 promoter, NRF2/ATF4 genetic knockdown, ferroptosis assays with class I and II inducers Cell cycle Medium 30907299
2022 Eleven high-occurrence non-catalytic mutations within BAP1's UCH domain significantly destabilize the domain, increase aggregation propensity, and cause allosteric destabilization at sites distant from the catalytic site as revealed by hydrogen-deuterium exchange mass spectrometry, providing a mechanism for how non-catalytic mutations impair BAP1 function. Multiplex spectroscopic analysis, thermodynamic assays, HDX-MS, aggregation assays for UCH domain mutants Journal of molecular biology Medium 35317997
2021 BAP1 deubiquitinase activity is required for ROS homeostasis, cell motility, and mitochondrial activity in mesothelioma cells; catalytically dead BAP1 fails to rescue these phenotypes. Monitoring intracellular ROS levels partly restores morphology and mitochondrial activity in BAP1-inactivated cells. Quantitative mass spectrometry (proteome), gene expression arrays, functional assays in BAP1-null/wt/catalytic-dead mesothelioma lines, ROS measurements Oncotarget Medium 29069806
2015 A BAP1 point mutation F170I (found in esophageal squamous cell carcinoma) markedly suppresses deubiquitinase and auto-deubiquitinase activity and causes cytoplasmic mislocalization of BAP1, preventing its nuclear tumor suppressor function; wild-type BAP1 induces TCEAL7 expression, which the F170I mutant cannot. Deubiquitinase activity assay of mutant vs wt BAP1, subcellular fractionation/localization studies, gene expression microarray, TCEAL7 induction assays Cancer science Medium 26081045
2021 BAP1 has a cell-intrinsic role in B lymphocyte development: Bap1 deletion in the B cell lineage causes depletion of large pre-B cells, transitional B cells, and mature B cells with broad transcriptional changes linked to cell cycle regulation, and BAP1 loss increases histone H2AK119ub levels at gene regulatory regions in pre-B cells. Conditional Bap1 KO (Bap1fl/fl mb1-Cre) mouse, flow cytometry of B cell populations, RNA-seq, ChIP-seq for BAP1 binding and H2AK119ub Frontiers in immunology Medium 33912157
2021 Co-occurrence of BAP1 deficiency and SF3B1 hotspot mutation induces cellular senescence and growth arrest in uveal melanoma cells, associated with downregulation of DNA-repair genes and impaired DNA damage response; this provides a mechanistic explanation for the mutual exclusivity of these mutations in uveal melanoma. Isogenic UM cell lines with BAP1 deletion and SF3B1 mutation, transcriptome analysis, DNA damage response assays, zebrafish xenograft invasion models, mouse xenograft growth assays Molecular oncology Medium 34706158

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 BAP1 links metabolic regulation of ferroptosis to tumour suppression. Nature cell biology 839 30202049
2013 BAP1 and cancer. Nature reviews. Cancer 518 23550303
2017 BAP1 regulates IP3R3-mediated Ca2+ flux to mitochondria suppressing cell transformation. Nature 334 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 308 24347639
2015 Loss of BAP1 function leads to EZH2-dependent transformation. Nature medicine 299 26437366
2012 BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs. Journal of translational medicine 240 22935333
2020 Biological Mechanisms and Clinical Significance of BAP1 Mutations in Human Cancer. Cancer discovery 238 32690542
2009 The deubiquitinating enzyme BAP1 regulates cell growth via interaction with HCF-1. The Journal of biological chemistry 226 19815555
2013 Tumours associated with BAP1 mutations. Pathology 224 23277170
2018 Comprehensive Study of the Clinical Phenotype of Germline BAP1 Variant-Carrying Families Worldwide. Journal of the National Cancer Institute 206 30517737
2015 BAP1 promotes breast cancer cell proliferation and metastasis by deubiquitinating KLF5. Nature communications 180 26419610
2016 BAP1/ASXL1 recruitment and activation for H2A deubiquitination. Nature communications 169 26739236
2017 Modeling Renal Cell Carcinoma in Mice: Bap1 and Pbrm1 Inactivation Drive Tumor Grade. Cancer discovery 148 28473526
2020 BAP1: Not just a BRCA1-associated protein. Cancer treatment reviews 144 32877777
2021 Roles and mechanisms of BAP1 deubiquitinase in tumor suppression. Cell death and differentiation 136 33462414
2017 BAP1 mutations in high-grade meningioma: implications for patient care. Neuro-oncology 133 28482042
2019 BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation. Nature communications 126 30664650
2019 Regulation of H2A ubiquitination and SLC7A11 expression by BAP1 and PRC1. Cell cycle (Georgetown, Tex.) 119 30907299
2015 Clear Cell Renal Cell Carcinoma Subtypes Identified by BAP1 and PBRM1 Expression. The Journal of urology 116 26300218
2018 Mutant ASXL1 cooperates with BAP1 to promote myeloid leukaemogenesis. Nature communications 111 30013160
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
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
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 83 28275095
2014 Germline BAP1 mutations predispose also to multiple basal cell carcinomas. Clinical genetics 83 25080371
2018 Overview of BAP1 cancer predisposition syndrome and the relationship to uveal melanoma. Journal of current ophthalmology 82 29988936
2016 Gene of the month: BAP1. Journal of clinical pathology 77 27235536
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
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 62 27181379
2017 BAP1, a tumor suppressor gene driving malignant mesothelioma. Translational lung cancer research 58 28713672
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 56 35459788
2022 PBRM1, SETD2 and BAP1 - the trinity of 3p in clear cell renal cell carcinoma. Nature reviews. Urology 56 36253570
2014 BAP1 and BRAFV600E expression in benign and malignant melanocytic proliferations. Human pathology 56 25479927
2016 Germline BAP1 alterations in familial uveal melanoma. Genes, chromosomes & cancer 54 27718540
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
2021 BAP1-Mutated Clear Cell Renal Cell Carcinoma. American journal of clinical pathology 48 33210135
2021 Estimation of the timing of BAP1 mutation in uveal melanoma progression. Scientific reports 47 33903674
2013 A BAP1 mutation in a Danish family predisposes to uveal melanoma and other cancers. PloS one 47 23977234
2023 BAP1 as a guardian of genome stability: implications in human cancer. Experimental & molecular medicine 46 37009801
2021 Roles of the BAP1 Tumor Suppressor in Cell Metabolism. Cancer research 46 33446574
2023 Clinical practice guidelines for the diagnosis and surveillance of BAP1 tumour predisposition syndrome. European journal of human genetics : EJHG 43 37607989
2023 Structural basis of histone H2A lysine 119 deubiquitination by Polycomb repressive deubiquitinase BAP1/ASXL1. Science advances 41 37556531
2021 BAP1/ASXL complex modulation regulates epithelial-mesenchymal transition during trophoblast differentiation and invasion. eLife 41 34170818
2020 BAP1: role in carcinogenesis and clinical implications. Translational lung cancer research 41 32206571
2018 BAP1 induces cell death via interaction with 14-3-3 in neuroblastoma. Cell death & disease 40 29686263
2015 Stabilization of MCRS1 by BAP1 prevents chromosome instability in renal cell carcinoma. Cancer letters 40 26300492
2020 Identifying BAP1 Mutations in Clear-Cell Renal Cell Carcinoma by CT Radiomics: Preliminary Findings. Frontiers in oncology 36 32185138
2020 BAP1 suppresses prostate cancer progression by deubiquitinating and stabilizing PTEN. Molecular oncology 36 33155366
2016 BAP1 suppresses lung cancer progression and is inhibited by miR-31. Oncotarget 36 26885612
2016 Loss of expression of BAP1 is very rare in non-small cell lung carcinoma. Pathology 34 27114369
2018 BAP1 regulation of the key adaptor protein NCoR1 is critical for γ-globin gene repression. Genes & development 33 30463901
2015 Analysis of BAP1 Germline Gene Mutation in Young Uveal Melanoma Patients. Ophthalmic genetics 32 25687217
2022 The expanding role of BAP1 in clear cell renal cell carcinoma. Human pathology 31 35932824
2020 CCR5 blockade inflames antitumor immunity in BAP1-mutant clear cell renal cell carcinoma. Journal for immunotherapy of cancer 31 32371459
2014 BAP1 has a survival role in cutaneous melanoma. The Journal of investigative dermatology 31 25521456
2020 The Tumor Suppressor BAP1 Regulates the Hippo Pathway in Pancreatic Ductal Adenocarcinoma. Cancer research 29 31988076
2020 Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network. Protein & cell 29 32683582
2019 BAP1 promotes stalled fork restart and cell survival via INO80 in response to replication stress. The Biochemical journal 29 31657441
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
2023 BAP1 promotes osteoclast function by metabolic reprogramming. Nature communications 26 37740028
2023 BAP1 is a novel regulator of HIF-1α. Proceedings of the National Academy of Sciences of the United States of America 25 36656861
2021 BAP1 antagonizes WWP1-mediated transcription factor KLF5 ubiquitination and inhibits autophagy to promote melanoma progression. Experimental cell research 25 33516665
2017 Modulating BAP1 expression affects ROS homeostasis, cell motility and mitochondrial function. Oncotarget 24 29069806
2015 Loss of BAP1 Expression in Basal Cell Carcinomas in Patients With Germline BAP1 Mutations. American journal of clinical pathology 24 25972334
2021 Co-occurrence of BAP1 and SF3B1 mutations in uveal melanoma induces cellular senescence. Molecular oncology 23 34706158
2016 Functional Link between BRCA1 and BAP1 through Histone H2A, Heterochromatin and DNA Damage Response. Current cancer drug targets 23 26517537
2015 A novel BAP1 mutation is associated with melanocytic neoplasms and thyroid cancer. Cancer genetics 23 26774355
2021 Novel insights into the BAP1-inactivated melanocytic tumor. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 21 34857909
2024 Tumor suppressor BAP1 suppresses disulfidptosis through the regulation of SLC7A11 and NADPH levels. Oncogenesis 19 39266549
2019 BAP1 in solid tumors. Future oncology (London, England) 19 31159579
2015 Somatic alteration and depleted nuclear expression of BAP1 in human esophageal squamous cell carcinoma. Cancer science 19 26081045
2023 Genetic screens reveal new targetable vulnerabilities in BAP1-deficient mesothelioma. Cell reports. Medicine 17 36657447
2023 Preventive and therapeutic opportunities: targeting BAP1 and/or HMGB1 pathways to diminish the burden of mesothelioma. Journal of translational medicine 17 37880686
2023 ITGB2-ICAM1 axis promotes liver metastasis in BAP1-mutated uveal melanoma with retained hypoxia and ECM signatures. Cellular oncology (Dordrecht, Netherlands) 17 38150154
2022 MBD5 and MBD6 stabilize the BAP1 complex and promote BAP1-dependent cancer. Genome biology 17 36180891
2022 Intrinsic Disorder in BAP1 and Its Association with Uveal Melanoma. Genes 17 36292588
2022 BAP1 in cancer: epigenetic stability and genome integrity. Discover oncology 16 36318367
2021 Intratumor Heterogeneity in Uveal Melanoma BAP-1 Expression. Cancers 16 33800007
2024 Multiple Onychopapillomas and BAP1 Tumor Predisposition Syndrome. JAMA dermatology 15 38759225
2022 Pyruvate dehydrogenase inactivation causes glycolytic phenotype in BAP1 mutant uveal melanoma. Oncogene 15 35046531
2022 Bap1/SMN axis in Dpp4+ skeletal muscle mesenchymal cells regulates the neuromuscular system. JCI insight 15 35603786
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 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 CHIP and BAP1 Act in Concert to Regulate INO80 Ubiquitination and Stability for DNA Replication. Molecules and cells 14 33658435
2021 The spectrum of tumors harboring BAP1 gene alterations. Cancer genetics 14 33866194
2025 FOXO3a-BAP1 axis regulates neuronal ferroptosis in early brain injury after subarachnoid hemorrhage. Redox biology 13 40080966
2023 BAP1 Loss Is Associated with Higher ASS1 Expression in Epithelioid Mesothelioma: Implications for Therapeutic Stratification. Molecular cancer research : MCR 13 36669126
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
2021 BAP1 loss augments sensitivity to BET inhibitors in cancer cells. Acta pharmacologica Sinica 13 34737422
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
2023 Targeting BAP1 with small compound inhibitor for colon cancer treatment. Scientific reports 12 36754982
2022 Diagnostic capacity of BAP1 and MTAP in cytology from effusions and biopsy in mesothelioma. Journal of the American Society of Cytopathology 12 35945149
2021 BAP1 and YY1 regulate expression of death receptors in malignant pleural mesothelioma. The Journal of biological chemistry 12 34597666

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