Affinage

KDM5B

Lysine-specific demethylase 5B · UniProt Q9UGL1

Length
1544 aa
Mass
175.7 kDa
Annotated
2026-06-10
100 papers in source corpus 42 papers cited in narrative 43 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KDM5B (PLU-1/JARID1B) is a nuclear, chromatin-associated histone demethylase that erases active H3K4 trimethyl marks to act primarily as a transcriptional repressor across development, stem cell maintenance, DNA repair, immune regulation, and cancer (PMID:17363312, PMID:18048344, PMID:17709396, PMID:10336460, PMID:14579128). Its catalytic core is a JmjC-domain Fe(II)/2-oxoglutarate-dependent dioxygenase that removes H3K4me3 and H3K4me2 with high affinity, and its active-site geometry has been resolved crystallographically and exploited by selective inhibitors (PMID:17363312, PMID:18048344, PMID:27214403, PMID:22420752). KDM5B reaches its targets through a combination of intrinsic chromatin readers and partner factors: its ARID domain binds CG-rich DNA, its PHD1 finger reads unmodified H3K4 while PHD3 reads H3K4me3, and it is directed to intragenic H3K36me3 regions via MRG15, focusing H3K4 methylation at promoters/enhancers and preventing cryptic transcription and lineage-inappropriate gene expression during ESC differentiation (PMID:17709396, PMID:24412361, PMID:21448134, PMID:22020125, PMID:24495580). It operates within multi-subunit repressive machinery, partnering with LSD1/NuRD-associated HDACs and PRC2 (via SUZ12), and serving as a corepressor for sequence-specific transcription factors including AR, ERα, TIEG1, and a TFAP2C/Myc complex at CDKN1A (PMID:17373667, PMID:21937684, PMID:24412361, PMID:22371483, PMID:24619877, PMID:18048344, PMID:21369698, PMID:20863814). Through promoter-specific H3K4 demethylation KDM5B represses defined targets—BRCA1 and metallothioneins, PTEN and PIK3CA to tune PI3K/AKT signaling, and developmental/lineage genes such as HOXA5, Runx2, and Foxa1—linking it to cell migration, angiogenesis, senescence, and cancer cell identity (PMID:17709396, PMID:25909289, PMID:32868382, PMID:26023081, PMID:26453309, PMID:24802759). Beyond catalysis, KDM5B has a demethylase-independent scaffolding role, recruiting SETDB1 to silence retroelements and restrain type-I interferon responses, and supporting anti-AML stemness repression through chromatin association rather than enzymatic activity (PMID:34671158, PMID:35217626). KDM5B is recruited to DNA double-strand breaks in a PARP1/macroH2A1.1-dependent manner to enable Ku70, BRCA1, and XRCC1 recruitment, and it shapes innate immunity by erasing H3K4me3 at Nfkbia and proinflammatory cytokine loci (PMID:24778210, PMID:29989047, PMID:36914768, PMID:33240782). Its abundance and chromatin occupancy are tuned post-translationally by PARP1 PARylation, CDK1 phosphorylation at Ser1456, TRAF6 K63-ubiquitination, and stabilization via USP7, USP38, and HSP90 (PMID:20832725, PMID:31776402, PMID:25596733, PMID:38287116, PMID:33240782, PMID:29989047).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2003 Medium

    Before its enzymatic role was known, KDM5B was shown to be a transcriptional corepressor recruited by developmental transcription factors, establishing it as a chromatin regulator embedded in repressive transcriptional programs.

    Evidence Yeast two-hybrid, co-IP, and VP-motif mutagenesis with BF-1 and PAX9 plus reporter assays

    PMID:12657635

    Open questions at the time
    • No molecular activity defined at this stage
    • VP-motif interaction surface on KDM5B not mapped
  2. 2007 High

    The defining discovery established KDM5B as a JmjC-domain Fe(II)/2-oxoglutarate-dependent dioxygenase that directly demethylates H3K4me3, converting a transcription cofactor into a defined enzymatic eraser of an active chromatin mark.

    Evidence In vitro demethylation assays, cofactor dependency, JmjC active-site mutagenesis, mass spectrometry

    PMID:17363312 PMID:18048344

    Open questions at the time
    • Genome-wide targeting rules not yet defined
    • Did not resolve catalytic vs. non-catalytic functions
  3. 2007 High

    Promoter-binding and direct target studies showed how KDM5B is targeted and what it represses, linking enzymatic H3K4me3 erasure to specific gene silencing including BRCA1 and metallothioneins, and to AR and HDAC corepressor partnerships.

    Evidence ChIP, microarray, EMSA/ARID motif mapping, co-IP with HDAC4 and AR, reporter assays

    PMID:17373667 PMID:17709396 PMID:18048344

    Open questions at the time
    • Causality between H3K4me3 loss and repression not separated from complex effects
    • HDAC/AR interactions from single labs
  4. 2010 High

    Post-translational control of KDM5B was first established, showing that PARP1 PARylation excludes KDM5B from promoters to protect H3K4me3, and that TIEG1 recruits it for TGF-β-related repression.

    Evidence ChIP, PARylation assays, RNAi, co-IP and domain mapping, RT-PCR

    PMID:20832725 PMID:20863814

    Open questions at the time
    • Stoichiometry and dynamics of PARylation in vivo unresolved
    • TIEG1 link is Medium-confidence single lab
  5. 2011 High

    Genome-scale and complex studies revealed how KDM5B is recruited and focuses H3K4 methylation, defining MRG15/H3K36me3-guided intragenic recruitment and LSD1/NuRD complex membership coupling H3K4 demethylation to repression.

    Evidence ChIP-seq, co-IP, H3K36me3 interaction assays, RNAi/RNA-seq, in vivo breast cancer xenograft

    PMID:21369698 PMID:21448134 PMID:21937684 PMID:22152480

    Open questions at the time
    • Relative contributions of intrinsic readers vs. partner-mediated recruitment not quantified
    • ERα/FOXP3 links Medium-confidence
  6. 2012 High

    KDM5B was placed within cell-cycle/senescence control, acting in the Rb pathway at E2F targets and forming a TFAP2C/Myc ternary complex requiring its demethylase activity to repress CDKN1A.

    Evidence Senescence-bypass genetic screen, ChIP, co-IP, demethylase-dead mutant, luciferase assays

    PMID:21980403 PMID:22371483 PMID:22615382

    Open questions at the time
    • Direct catalytic requirement at E2F targets not isolated
    • Generalizability beyond CDKN1A unclear
  7. 2014 High

    Mechanistic dissection of chromatin reading and a non-transcriptional role emerged: PHD1 reads H3K4me0 and PHD3 reads H3K4me3 to control migration, KDM5B co-localizes with H3K4me3 to focus methylation, it links to PRC2 via SUZ12, and it is recruited to DNA double-strand breaks to enable repair factor loading.

    Evidence Peptide pulldowns, domain mutagenesis, ChIP-seq, in vitro SUZ12 pulldown, laser micro-irradiation, γH2AX foci, clonogenic survival

    PMID:24412361 PMID:24495580 PMID:24619877 PMID:24778210 PMID:24802759

    Open questions at the time
    • How DSB recruitment integrates with promoter functions unresolved
    • PRC2/GATA3 links Medium-confidence single labs
  8. 2015 High

    ESC/differentiation and tissue-specific roles consolidated KDM5B as a lineage gatekeeper and oncogenic node, demethylating H3K4 at developmental loci (HOXA5, Runx2, Reln) and at PTEN to drive PI3K/AKT-dependent cancer phenotypes, with additional ubiquitin-based regulation by TRAF6/SKP2.

    Evidence Conditional KO mice, ChIP, catalytic-inactive mutants, angiogenic/differentiation assays, in vivo ubiquitination assays

    PMID:22020125 PMID:25596733 PMID:25909289 PMID:26023081 PMID:26453309 PMID:26739753

    Open questions at the time
    • Tissue-specific targeting determinants not unified
    • Several cancer target links are Medium-confidence
  9. 2016 High

    Structural and kinetic characterization of the catalytic core defined the 2-oxoglutarate binding site and selectivity determinants and enabled selective inhibitors, providing a chemical-biology framework for the enzyme.

    Evidence X-ray co-crystal structures with three inhibitor chemotypes, enzymatic inhibition, kinetic characterization, cellular H3K4me3 assays

    PMID:22420752 PMID:27214403

    Open questions at the time
    • Full-length regulatory domain architecture not captured
    • Structures of chromatin-bound complex absent
  10. 2021 High

    A demethylase-independent scaffolding function was established, with KDM5B recruiting SETDB1 to silence retroelements and suppress type-I interferon responses, expanding its role beyond catalysis into immune evasion.

    Evidence Co-IP, retroelement de-repression, innate immune reporters, catalytic mutant, mouse melanoma models

    PMID:34671158

    Open questions at the time
    • Mechanism of SETDB1 recruitment domain mapping incomplete
    • Interplay between catalytic and scaffold modes in same cell unresolved
  11. 2023 High

    Innate immune and inflammatory roles were mechanistically anchored, with KDM5B erasing H3K4me3 and reducing accessibility at Nfkbia to enable NF-κB activation, and USP38-coupled recruitment to cytokine promoters, defining its pro-inflammatory chromatin function.

    Evidence ChIP-seq, ATAC-seq, RNAi, ubiquitination assays, mouse arthritis/endotoxin/RSV models

    PMID:26083387 PMID:33240782 PMID:36914768

    Open questions at the time
    • How a repressor of IκBα coexists with cytokine-promoter recruitment context-dependently unclear
  12. 2024 Medium

    Deubiquitinase-mediated stabilization linked to therapy resistance was established, with USP7 stabilizing KDM5B to repress ZBTB16 and confer cisplatin resistance, alongside HSP90- and USP38-mediated protection from degradation.

    Evidence Co-IP, ubiquitination assays, ChIP, shRNA, in vivo xenograft

    PMID:29989047 PMID:38287116

    Open questions at the time
    • Single-lab target links
    • Generalizability of USP7-KDM5B axis beyond nasopharyngeal carcinoma untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How KDM5B's catalytic versus scaffolding modes are selected at individual loci, and how its many post-translational modifiers and partner complexes are coordinated in a given cell state, remains unresolved.
  • No unified model integrating reader domains, partner complexes, and PTMs for context-specific targeting
  • Structure of KDM5B engaged with a full repressive complex on nucleosomes lacking
  • Determinants distinguishing repressed vs. activated outcomes per locus undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016491 oxidoreductase activity 4 GO:0140110 transcription regulator activity 3 GO:0042393 histone binding 2 GO:0060090 molecular adaptor activity 2 GO:0003677 DNA binding 1
Localization
GO:0000228 nuclear chromosome 4 GO:0005654 nucleoplasm 2 GO:0005634 nucleus 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-168256 Immune System 4 R-HSA-4839726 Chromatin organization 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-73894 DNA Repair 2
Partners
ARESR1HDAC1LSD1MRG15SETDB1SUZ12TFAP2C
Complex memberships
LSD1/NuRD complexPRC2 (via SUZ12)

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 PLU-1/KDM5B is a histone demethylase that directly removes the trimethyl mark from H3K4 (H3K4me3), demonstrated by in vitro biochemical demethylation assays and active-site mutagenesis of the JmjC domain. In vitro histone demethylation assay, JmjC domain mutagenesis, mass spectrometry Molecular cell High 17363312 18048344
2007 KDM5B demethylase activity requires the JmjC domain and uses Fe(II) and alpha-ketoglutarate as cofactors, classifying it as a 2-oxoglutarate-dependent dioxygenase. In vitro biochemical assay with cofactor supplementation and chelation; JmjC domain mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 18048344
2007 KDM5B associates with the androgen receptor (AR) and regulates its transcriptional activity, demonstrated by co-immunoprecipitation and reporter assays. Co-immunoprecipitation, transcriptional reporter assay Proceedings of the National Academy of Sciences of the United States of America Medium 18048344
2010 PARP-1 inhibits KDM5B demethylase activity by PARylating KDM5B and excluding it from promoters, thereby protecting H3K4me3 marks and maintaining a permissive chromatin environment for transcription. ChIP, RNAi knockdown, PARylation assay, promoter occupancy analysis Molecular cell High 20832725
2003 KDM5B (PLU-1) interacts directly with developmental transcription factors BF-1 and PAX9 via a conserved VP motif in those proteins; this interaction requires specific residues in the VP motif (demonstrated by site-directed mutagenesis) and enhances transcriptional repression. Yeast two-hybrid, co-immunoprecipitation, site-directed mutagenesis, reporter assay The Journal of biological chemistry Medium 12657635
2007 KDM5B directly represses target genes including BRCA1 and metallothionein genes (MT1H, MT1F, MT1X) by binding their promoters and reducing H3K4me3 levels, demonstrated by ChIP and siRNA knockdown with microarray analysis. Chromatin immunoprecipitation (ChIP), microarray, RNAi knockdown, overexpression Molecular and cellular biology High 17709396
2007 KDM5B binds CG-rich DNA through its ARID domain, with the GCACA/C motif identified as a consensus binding sequence. EMSA, mutagenesis, reporter assay Molecular and cellular biology Medium 17709396
2007 KDM5B directly interacts with class I and class IIa histone deacetylases (HDACs), with two PHD domains of KDM5B binding a domain in the 5' region of HDAC4 overlapping the MEF-2 binding region. Co-immunoprecipitation, domain mapping, co-localization in MAD bodies upon co-transfection International journal of cancer Medium 17373667
2011 KDM5B is a physical component of the LSD1/NuRD complex; KDM5B and LSD1 act sequentially and coordinately to demethylate H3K4, repressing the CCL14 chemokine pathway to suppress angiogenesis and metastasis in breast cancer. Co-immunoprecipitation, ChIP, genome-wide transcriptional analysis, in vivo xenograft Cancer research High 21937684
2014 KDM5B PHD1 finger binds unmodified histone H3 (H3K4me0) with high specificity, whereas PHD3 finger preferentially binds H3K4me3; PHD1-H3K4me0 interaction is essential for KDM5B's role in inhibiting cell migration. Peptide pulldown, histone binding assays, domain mutagenesis, RNA-seq, migration assay Cell reports High 24412361
2014 KDM5B associates with components of the NuRD complex (including HDAC1) and cooperates with HDAC1 for gene repression, demonstrated by biochemical co-immunoprecipitation. Co-immunoprecipitation Cell reports Medium 24412361
2011 KDM5B is recruited to intragenic regions via interaction with the chromodomain protein MRG15, which recognizes H3K36me3; KDM5B depletion leads to increased intragenic H3K4me3 and cryptic intragenic transcription, impairing transcriptional elongation of self-renewal genes. ChIP-seq, Co-immunoprecipitation, RNAi knockdown with RNA-seq, H3K36me3 interaction assay The EMBO journal High 21448134
2011 Jarid1b/KDM5B localizes predominantly to transcription start sites of developmental regulator genes; its depletion leads to global increases in H3K4me3 and failure to silence lineage-inappropriate genes during ESC neural differentiation. Genome-wide ChIP-seq (location analysis), RNAi knockdown, differentiation assays The EMBO journal High 22020125
2014 KDM5B co-localizes with H3K4me3 at promoters and enhancers of active genes; its depletion leads to spreading of H3K4 methylation into gene bodies and enhancer shores, linking KDM5B to focusing of H3K4 methylation. ChIP-seq, RNAi knockdown Genome biology High 24495580
2014 KDM5B becomes enriched at DNA double-strand break (DSB) sites in a PARP1- and macroH2A1.1-dependent manner, and is required for efficient DSB repair and for recruitment of Ku70 and BRCA1 to damage sites. Laser micro-irradiation, immunofluorescence, RNAi knockdown, γH2AX foci, clonogenic survival Proceedings of the National Academy of Sciences of the United States of America High 24778210
2012 Jarid1b/KDM5B is a component of the Rb pathway: depletion of Jarid1b phenocopies Rb1 knockdown, and Jarid1b associates with E2F-target gene promoters during senescence to mediate H3K4 demethylation-dependent gene silencing. Functional genetic screen for senescence bypass, RNAi, ChIP, E2F-target promoter analysis Proceedings of the National Academy of Sciences of the United States of America Medium 21980403 22615382
2012 KDM5B forms a ternary complex with TFAP2C and Myc at the CDKN1A proximal promoter; all three factors collaborate for optimal CDKN1A repression, which requires the AP-2 binding site at -111/-103 and KDM5B demethylase activity. Co-immunoprecipitation, ChIP, luciferase reporter assay, domain mapping, demethylase-dead mutant Molecular and cellular biology High 22371483
2016 Crystal structures of the catalytic core of human KDM5B in complex with three distinct inhibitor chemotypes revealed the 2-oxoglutarate binding site geometry and selectivity determinants; KDM5B active site shares hybrid features with KDM4 and KDM6 families. X-ray crystallography, in vitro enzymatic inhibition assays, cellular H3K4me3 elevation Nature chemical biology High 27214403
2012 Recombinant KDM5B catalytic core demethylates H3K4me3 and H3K4me2 in vitro with an apparent Km of 0.5 µM for H3K4me3 peptide substrate; 2,4-pyridinedicarboxylic acid (2,4-PDCA) inhibits KDM5B both in vitro and in cells. In vitro enzymatic assay with recombinant protein, kinetic characterization, cell-based inhibitor assay The FEBS journal High 22420752
2021 KDM5B recruits the H3K9 methyltransferase SETDB1 to silence endogenous retroelements in a demethylase-independent manner; derepression of retroelements activates cytosolic RNA/DNA sensing and type-I interferon responses leading to tumor rejection. RNAi knockdown, Co-immunoprecipitation (KDM5B-SETDB1), MMVL30 retroelement de-repression assay, innate immune reporter assays, mouse melanoma models Nature High 34671158
2010 KDM5B acts as a corepressor for the transcription factor TIEG1/KLF10; the repression domains of TIEG1 bind the C-terminus of KDM5B, and KDM5B knockdown increases Smad7 mRNA levels, linking KDM5B to TGF-β signaling repression. Co-immunoprecipitation, domain mapping, RNAi knockdown, RT-PCR Biochemical and biophysical research communications Medium 20863814
2011 FOXP3 activates target genes by recruiting MOF (histone acetyltransferase) and simultaneously displacing KDM5B (PLU-1) from promoters, increasing both H4K16 acetylation and H3K4me3. ChIP, RNAi, reporter assay, Co-immunoprecipitation Molecular cell Medium 22152480
2014 KDM5B associates with PRC2 via direct interaction between KDM5B and the SUZ12 component; co-occupancy at RA-responsive genes leads to a biphasic regulatory effect on retinoic acid signaling through decoupled H3K4me3 demethylation and PRC2-antagonizing activities. Co-immunoprecipitation, in vitro pulldown, ChIP, reporter assay Journal of cellular biochemistry Medium 24619877
2011 JARID1B epigenetically represses the tumor suppressor microRNA let-7e by binding to its promoter region and removing the H3K4me3 mark, leading to cyclin D1 upregulation and G1-to-S cell cycle progression in breast cancer cells. ChIP, RNAi, cell cycle analysis, luciferase reporter, RT-PCR The Journal of biological chemistry Medium 21969366
2015 KDM5B represses H3K4me3 at the PTEN promoter, reducing PTEN transcription and thereby activating the downstream PI3K/AKT pathway to promote hepatocellular carcinoma metastasis. ChIP, overexpression, RNAi knockdown, rescue with PTEN overexpression, in vivo xenograft Oncotarget Medium 25909289
2015 KDM5B represses expression of H3K4me2/3 at the Runx2 P1 promoter during myogenic differentiation of mesenchymal cells; KDM5B knockdown (but not UTX or NO66 knockdown) prevents repression of this promoter, identifying KDM5B as a specific component of the epigenetic switch controlling osteoblast vs. myoblast lineage commitment. RNAi knockdown, ChIP, differentiation assays, epistasis (UTX/NO66 controls) The Journal of biological chemistry Medium 26453309
2015 USP38 deubiquitinase couples histone ubiquitination to H3K4 demethylation by interacting with KDM5B: USP38 removes monoubiquitin from H2BK120, enabling KDM5B recruitment to promoters of proinflammatory cytokine genes (Il6, Il23a); additionally, USP38 physically binds KDM5B and prevents its proteasomal degradation. Co-immunoprecipitation, ChIP, RNAi, ubiquitination assay, mouse endotoxin shock model Advanced science High 33240782
2015 SKP2 modulates JARID1B ubiquitination: TRAF6-mediated K63-linked ubiquitination reduces KDM5B demethylase activity and increases H3K4me3; SKP2 antagonizes TRAF6-mediated ubiquitination, thereby increasing KDM5B demethylase activity. Co-immunoprecipitation, in vivo ubiquitination assay, mouse knockout models, mass spectrometry Oncotarget Medium 25596733
2018 KDM5B is phosphorylated at Ser1456 by CDK1; this phosphorylation attenuates KDM5B occupancy on promoters of pluripotency genes (SOX2, NANOG), reducing their repression and modulating stem cell population in triple-negative breast cancer. Mass spectrometry phosphorylation mapping, ChIP, CDK1 kinase assay, RNAi, stem cell marker analysis Scientific reports Medium 31776402
2018 KDM5B demethylates H3K4 at the XRCC1 locus to facilitate XRCC1 recruitment to DNA damage sites, and HSP90 protects KDM5B from ubiquitin-dependent proteasomal degradation by forming a complex with it. Co-immunoprecipitation, mass spectrometry, ChIP, γH2AX co-localization, knockdown, HSP90 inhibitor degradation assay International journal of biological sciences Medium 29989047
2023 In activated macrophages, KDM5B is selectively recruited to the Nfkbia (IκBα) promoter where it erases H3K4me3 and decreases chromatin accessibility, thereby suppressing IκBα expression and enabling full NF-κB activation and pro-inflammatory cytokine production. Genome-wide ChIP-seq, ATAC-seq, RNAi knockdown, mouse arthritis and endotoxin models Cell death and differentiation High 36914768
2020 KDM5B directly binds the PIK3CA promoter and its loss results in reduced P110α and PIP3 levels; KDM5B controls PI3K/AKT hyperactivation in prostate cancer, demonstrated in Pten/Kdm5b double-mutant mouse models. ChIP, prostate-specific conditional knockout mouse model, western blot for PI3K pathway components, in vitro knockdown/overexpression Cancer research High 32868382
2022 KDM5B binds to the Atf3 (ATF3) promoter and inhibits ATF3 expression by demethylating H3K4me2/3; loss of KDM5B de-represses ATF3, suppressing TGF-β-driven cardiac fibrosis. ChIP, RNAi knockdown, mouse myocardial infarction and pressure overload models, western blot Experimental & molecular medicine Medium 36481938
2014 KDM5B is required for GATA3 recruitment to the Foxa1 promoter to activate Foxa1 expression; loss of KDM5B reduces FOXA1 and ERα in mammary epithelial cells, impairing ductal development. ChIP for GATA3, KO mouse model, gene expression analysis, mammary phenotyping The Journal of biological chemistry Medium 24802759
2015 KDM5B directly demethylates H3K4me3 at the HOXA5 promoter in endothelial cells, suppressing HOXA5 expression to maintain angiogenic capacity; endothelial-specific Jarid1b knockout attenuates retinal angiogenesis. ChIP, endothelial-specific conditional KO mouse (tamoxifen-inducible), shRNA knockdown, angiogenic sprouting assay, overexpression of catalytic-inactive mutant Arteriosclerosis, thrombosis, and vascular biology High 26023081
2015 KDM5B inhibits IFN-β and innate cytokine production in dendritic cells upon RSV infection; conditional deletion of Kdm5b in CD11c+ DCs results in higher IFN-γ and reduced Th2 cytokines in vivo. DC-specific conditional KO mouse (Kdm5bfl/fl-CD11c-Cre), siRNA knockdown, cytokine measurement, adoptive transfer model PLoS pathogens Medium 26083387
2013 Jarid1b/KDM5B is identified as a negative regulator of hematopoietic stem cell (HSC) activity: decreased Jarid1b levels expand HSCs in vitro while preserving lymphomyeloid differentiation potential; HSC regulators (Hoxa7, Hoxa9, Hoxa10, Hes1, Gata2) are upregulated upon Jarid1b knockdown. In vivo RNAi-based functional screen, in vitro HSC expansion assay, RNA sequencing Blood Medium 23777767
2024 The deubiquitinase USP7 deubiquitinates and stabilizes KDM5B protein; KDM5B then reduces H3K4me3 at the ZBTB16 promoter, repressing ZBTB16 and increasing TOP2A expression to confer cisplatin resistance in nasopharyngeal carcinoma. Co-immunoprecipitation, ubiquitination assay, ChIP, shRNA knockdown, in vivo xenograft Cell death and differentiation Medium 38287116
2022 In AML, Kdm5b directly binds and represses stemness gene promoters; the anti-AML effect relies on KDM5B's chromatin association/scaffold functions rather than its demethylase catalytic activity, as demonstrated using catalytic mutants. RNA-seq, ChIP-seq, CUT&RUN, catalytic mutant rescue experiments, KDM5B overexpression vs depletion in AML cells Proceedings of the National Academy of Sciences of the United States of America Medium 35217626
1999 PLU-1/KDM5B protein is nuclear and localizes in discrete foci, demonstrated by transient transfection of MYC-tagged PLU-1 followed by immunofluorescence; subcellular fractionation confirmed chromatin association in somatic and meiotic cells. Immunofluorescence of tagged protein, biochemical cell fractionation The Journal of biological chemistry Medium 10336460 14579128
2011 KDM5B interacts with estrogen receptor alpha (ERα) and knockdown of KDM5B in MCF-7 cells dramatically decreases estrogen-stimulated tumor growth in vivo; KDM5B also regulates ERα target gene expression (e.g., progesterone receptor). Co-immunoprecipitation (tagged ERα and JARID1B), shRNAi knockdown, in vivo xenograft International journal of oncology Medium 21369698
2019 KDM5B inhibits expression of miR-448 by demethylating H3K4me3 at the miR-448 promoter, which in turn upregulates YTHDF3 and ITGA6 to promote HCC progression. ChIP, luciferase reporter (YTHDF3 3'UTR), RT-qPCR, knockdown/overexpression, in vivo xenograft Journal of cellular and molecular medicine Medium 33829656
2013 Jarid1b/KDM5B in mouse ESCs inhibits H3K4me3 at the Kdm5b-bound Reln (reelin) promoter; depletion of Kdm5b in adult SVZ neural stem cells increases H3K4me3 at the Reln locus, upregulates Reln expression and secretion, and enhances downstream Dab1 phosphorylation and migratory behavior. ChIP (H3K4me3 at Reln promoter), shRNA knockdown, immunofluorescence, extracellular reelin ELISA, phospho-Dab1 western blot, migration assay with reelin-blocking antibody rescue Molecular biology of the cell Medium 26739753

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation. Molecular cell 391 17363312
2007 JARID1B is a histone H3 lysine 4 demethylase up-regulated in prostate cancer. Proceedings of the National Academy of Sciences of the United States of America 308 18048344
2010 PARP-1 regulates chromatin structure and transcription through a KDM5B-dependent pathway. Molecular cell 272 20832725
2021 KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements. Nature 222 34671158
1999 A novel gene (PLU-1) containing highly conserved putative DNA/chromatin binding motifs is specifically up-regulated in breast cancer. The Journal of biological chemistry 197 10336460
2014 JARID1B is a luminal lineage-driving oncogene in breast cancer. Cancer cell 163 24937458
2011 Jarid1b targets genes regulating development and is involved in neural differentiation. The EMBO journal 162 22020125
2016 Structural analysis of human KDM5B guides histone demethylase inhibitor development. Nature chemical biology 157 27214403
2011 Binding of the JmjC demethylase JARID1B to LSD1/NuRD suppresses angiogenesis and metastasis in breast cancer cells by repressing chemokine CCL14. Cancer research 152 21937684
2014 The histone-H3K4-specific demethylase KDM5B binds to its substrate and product through distinct PHD fingers. Cell reports 140 24412361
2011 KDM5B regulates embryonic stem cell self-renewal and represses cryptic intragenic transcription. The EMBO journal 137 21448134
2011 PLU-1/JARID1B/KDM5B is required for embryonic survival and contributes to cell proliferation in the mammary gland and in ER+ breast cancer cells. International journal of oncology 131 21369698
2012 H3K4 demethylation by Jarid1a and Jarid1b contributes to retinoblastoma-mediated gene silencing during cellular senescence. Proceedings of the National Academy of Sciences of the United States of America 126 22615382
2014 Histone demethylase KDM5B is a key regulator of genome stability. Proceedings of the National Academy of Sciences of the United States of America 121 24778210
2014 KDM5B focuses H3K4 methylation near promoters and enhancers during embryonic stem cell self-renewal and differentiation. Genome biology 117 24495580
2002 PLU-1 nuclear protein, which is upregulated in breast cancer, shows restricted expression in normal human adult tissues: a new cancer/testis antigen? International journal of cancer 117 12237901
2007 Functional analysis of the transcription repressor PLU-1/JARID1B. Molecular and cellular biology 106 17709396
2013 The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3. PLoS genetics 105 23637629
2016 Aberrant KDM5B expression promotes aggressive breast cancer through MALAT1 overexpression and downregulation of hsa-miR-448. BMC cancer 103 26917489
2008 The histone demethylase KDM5b/JARID1b plays a role in cell fate decisions by blocking terminal differentiation. Molecular and cellular biology 99 18591252
2018 KDM5B is a master regulator of the H3K4-methylome in stem cells, development and cancer. Seminars in cancer biology 94 30448242
2007 Breast cancer associated transcriptional repressor PLU-1/JARID1B interacts directly with histone deacetylases. International journal of cancer 81 17373667
2003 Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9. The Journal of biological chemistry 80 12657635
2011 Jumonji/ARID1 B (JARID1B) protein promotes breast tumor cell cycle progression through epigenetic repression of microRNA let-7e. The Journal of biological chemistry 79 21969366
2019 KDM5B promotes breast cancer cell proliferation and migration via AMPK-mediated lipid metabolism reprogramming. Experimental cell research 76 30978340
2015 RSV-Induced H3K4 Demethylase KDM5B Leads to Regulation of Dendritic Cell-Derived Innate Cytokines and Exacerbates Pathogenesis In Vivo. PLoS pathogens 71 26083387
2015 JARID1B promotes metastasis and epithelial-mesenchymal transition via PTEN/AKT signaling in hepatocellular carcinoma cells. Oncotarget 68 25909289
2015 Epigenetic Control of the Bone-master Runx2 Gene during Osteoblast-lineage Commitment by the Histone Demethylase JARID1B/KDM5B. The Journal of biological chemistry 68 26453309
2012 Histone demethylase KDM5B collaborates with TFAP2C and Myc to repress the cell cycle inhibitor p21(cip) (CDKN1A). Molecular and cellular biology 68 22371483
2008 RBP2-H1/JARID1B is a transcriptional regulator with a tumor suppressive potential in melanoma cells. International journal of cancer 66 17973255
2012 Studies of H3K4me3 demethylation by KDM5B/Jarid1B/PLU1 reveals strong substrate recognition in vitro and identifies 2,4-pyridine-dicarboxylic acid as an in vitro and in cell inhibitor. The FEBS journal 64 22420752
2017 miR424-5p functions as an anti-oncogene in cervical cancer cell growth by targeting KDM5B via the Notch signaling pathway. Life sciences 63 28082020
2011 FOXP3 orchestrates H4K16 acetylation and H3K4 trimethylation for activation of multiple genes by recruiting MOF and causing displacement of PLU-1. Molecular cell 62 22152480
2013 Extended self-renewal and accelerated reprogramming in the absence of Kdm5b. Molecular and cellular biology 60 24100015
2013 RNAi screen identifies Jarid1b as a major regulator of mouse HSC activity. Blood 58 23777767
2014 KDM5B is overexpressed in gastric cancer and is required for gastric cancer cell proliferation and metastasis. American journal of cancer research 56 25628922
2018 KDM5B demethylates H3K4 to recruit XRCC1 and promote chemoresistance. International journal of biological sciences 55 29989047
2018 Hypoxia Promotes Resistance to EGFR Inhibition in NSCLC Cells via the Histone Demethylases, LSD1 and PLU-1. Molecular cancer research : MCR 54 29934325
2015 Silencing JARID1B suppresses oncogenicity, stemness and increases radiation sensitivity in human oral carcinoma. Cancer letters 54 26184998
2020 USP38 Couples Histone Ubiquitination and Methylation via KDM5B to Resolve Inflammation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 52 33240782
2015 JARID1B Expression Plays a Critical Role in Chemoresistance and Stem Cell-Like Phenotype of Neuroblastoma Cells. PloS one 52 25951238
2013 Depletion of JARID1B induces cellular senescence in human colorectal cancer. International journal of oncology 50 23354547
2015 Transcriptional Regulation of JARID1B/KDM5B Histone Demethylase by Ikaros, Histone Deacetylase 1 (HDAC1), and Casein Kinase 2 (CK2) in B-cell Acute Lymphoblastic Leukemia. The Journal of biological chemistry 49 26655717
2015 SKP2 inactivation suppresses prostate tumorigenesis by mediating JARID1B ubiquitination. Oncotarget 48 25596733
2010 Histone demethylase JARID1B/KDM5B is a corepressor of TIEG1/KLF10. Biochemical and biophysical research communications 48 20863814
2018 KDM5B Promotes Drug Resistance by Regulating Melanoma-Propagating Cell Subpopulations. Molecular cancer therapeutics 47 30523048
2013 Androgen receptor activation by polychlorinated biphenyls: epigenetic effects mediated by the histone demethylase Jarid1b. Epigenetics 47 23907094
2016 JARID1B Enables Transit between Distinct States of the Stem-like Cell Population in Oral Cancers. Cancer research 46 27488530
2014 Histone demethylase jumonji AT-rich interactive domain 1B (JARID1B) controls mammary gland development by regulating key developmental and lineage specification genes. The Journal of biological chemistry 45 24802759
2014 Overexpressed KDM5B is associated with the progression of glioma and promotes glioma cell growth via downregulating p21. Biochemical and biophysical research communications 45 25450384
2020 KDM5B Is Essential for the Hyperactivation of PI3K/AKT Signaling in Prostate Tumorigenesis. Cancer research 43 32868382
2024 Deubiquitinase USP7 stabilizes KDM5B and promotes tumor progression and cisplatin resistance in nasopharyngeal carcinoma through the ZBTB16/TOP2A axis. Cell death and differentiation 42 38287116
2018 Lysine demethylase 5B (KDM5B): A potential anti-cancer drug target. European journal of medicinal chemistry 42 30343192
2015 MiR-29a suppresses prostate cell proliferation and induces apoptosis via KDM5B protein regulation. International journal of clinical and experimental medicine 42 26131109
2011 The histone demethylase Jarid1b (Kdm5b) is a novel component of the Rb pathway and associates with E2f-target genes in MEFs during senescence. PloS one 41 21980403
2020 Histone Demethylase KDM5B as a Therapeutic Target for Cancer Therapy. Cancers 39 32751840
2023 Histone demethylase KDM5B licenses macrophage-mediated inflammatory responses by repressing Nfkbia transcription. Cell death and differentiation 38 36914768
2019 SNHG1 promotes malignant biological behaviors of glioma cells via microRNA-154-5p/miR-376b-3p- FOXP2- KDM5B participating positive feedback loop. Journal of experimental & clinical cancer research : CR 37 30728054
2021 KDM5B promotes self-renewal of hepatocellular carcinoma cells through the microRNA-448-mediated YTHDF3/ITGA6 axis. Journal of cellular and molecular medicine 35 33829656
2022 Loss of KDM5B ameliorates pathological cardiac fibrosis and dysfunction by epigenetically enhancing ATF3 expression. Experimental & molecular medicine 34 36481938
2018 Targeting histone demethylases KDM5A and KDM5B in AML cancer cells: A comparative view. Leukemia research 34 29602065
2015 The histone demethylase Jarid1b is required for hematopoietic stem cell self-renewal in mice. Blood 34 25655602
2022 A PRC2-Kdm5b axis sustains tumorigenicity of acute myeloid leukemia. Proceedings of the National Academy of Sciences of the United States of America 33 35217626
2016 miR-194 inhibits gastric cancer cell proliferation and tumorigenesis by targeting KDM5B. European review for medical and pharmacological sciences 33 27874950
2015 Epigenetic Regulation of Angiogenesis by JARID1B-Induced Repression of HOXA5. Arteriosclerosis, thrombosis, and vascular biology 32 26023081
2003 PLU-1, a transcriptional repressor and putative testis-cancer antigen, has a specific expression and localisation pattern during meiosis. Chromosoma 32 14579128
2019 Targeting the H3K4 Demethylase KDM5B Reprograms the Metabolome and Phenotype of Melanoma Cells. The Journal of investigative dermatology 31 31229500
2019 JARID1B expression and its function in DNA damage repair are tightly regulated by miRNAs in breast cancer. Cancer science 30 30588710
2015 JARID1B modulates lung cancer cell proliferation and invasion by regulating p53 expression. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 30 25877751
2013 Jumonji/Arid1b (Jarid1b) protein modulates human esophageal cancer cell growth. Molecular and clinical oncology 30 24649241
2020 Discovery of pyrazole derivatives as cellular active inhibitors of histone lysine specific demethylase 5B (KDM5B/JARID1B). European journal of medicinal chemistry 29 32155529
2022 KDM5B promotes tumorigenesis of Ewing sarcoma via FBXW7/CCNE1 axis. Cell death & disease 28 35428764
2020 Histone Lysine Demethylases KDM5B and KDM5C Modulate Genome Activation and Stability in Porcine Embryos. Frontiers in cell and developmental biology 27 32211412
2019 Small Molecule Inhibitors of KDM5 Histone Demethylases Increase the Radiosensitivity of Breast Cancer Cells Overexpressing JARID1B. Molecules (Basel, Switzerland) 27 31060229
2019 Investigation of the potential theranostic role of KDM5B/miR-29c signaling axis in paclitaxel resistant endometrial carcinoma. Gene 26 30658067
2018 Novel KDM5B splice variants identified in patients with developmental disorders: Functional consequences. Gene 26 30217758
2022 Drawing a line between histone demethylase KDM5A and KDM5B: their roles in development and tumorigenesis. Experimental & molecular medicine 25 36509829
2019 Inhibition of the histone demethylase, KDM5B, directly induces re-expression of tumor suppressor protein HEXIM1 in cancer cells. Breast cancer research : BCR 25 31805991
2014 Coordinated regulation of retinoic acid signaling pathway by KDM5B and polycomb repressive complex 2. Journal of cellular biochemistry 25 24619877
2020 JARID1B promotes colorectal cancer proliferation and Wnt/β-catenin signaling via decreasing CDX2 level. Cell communication and signaling : CCS 24 33109187
2019 The Lysine Demethylase KDM5B Regulates Islet Function and Glucose Homeostasis. Journal of diabetes research 24 31467927
2017 Hepatitis B virus X protein induces hepatic stem cell-like features in hepatocellular carcinoma by activating KDM5B. World journal of gastroenterology 24 28566884
2016 Inhibition of the histone demethylase Kdm5b promotes neurogenesis and derepresses Reln (reelin) in neural stem cells from the adult subventricular zone of mice. Molecular biology of the cell 23 26739753
2022 Discovery of Novel Pyrazole-Based KDM5B Inhibitor TK-129 and Its Protective Effects on Myocardial Remodeling and Fibrosis. Journal of medicinal chemistry 21 36112701
2019 Phosphorylation of the histone demethylase KDM5B and regulation of the phenotype of triple negative breast cancer. Scientific reports 21 31776402
2016 Original Research: miR-194 inhibits proliferation and invasion and promotes apoptosis by targeting KDM5B in esophageal squamous cell carcinoma cells. Experimental biology and medicine (Maywood, N.J.) 21 27480251
2015 Immunohistochemical detection and clinicopathological significance of JARID1B/KDM5B and P16 expression in invasive ductal carcinoma of the breast. Genetics and molecular research : GMR 20 26125737
2023 The KDM5B and KDM1A lysine demethylases cooperate in regulating androgen receptor expression and signalling in prostate cancer. Frontiers in cell and developmental biology 19 37152294
2016 Overexpression of JARID1B promotes differentiation via SHIP1/AKT signaling in human hypopharyngeal squamous cell carcinoma. Cell death & disease 19 27584795
2013 JARID1B expression in human melanoma and benign melanocytic skin lesions. Melanoma research 19 23262439
2013 Connexin 26 is down-regulated by KDM5B in the progression of bladder cancer. International journal of molecular sciences 19 23579952
2002 Characterisation and developmental expression of mouse Plu-1, a homologue of a human nuclear protein (PLU-1) which is specifically up-regulated in breast cancer. Gene expression patterns : GEP 19 12617814
2025 Epstein-Barr virus hijacks histone demethylase machinery to drive epithelial malignancy progression through KDM5B upregulation. Signal transduction and targeted therapy 17 40059116
2022 Alcohol-associated fibrosis in females is mediated by female-specific activation of lysine demethylases KDM5B and KDM5C. Hepatology communications 17 35468265
2021 MiR-374b-5p inhibits KDM5B-induced epithelial-mesenchymal transition in pancreatic cancer. American journal of cancer research 17 34522457
2020 Histone lysine demethylase KDM5B maintains chronic myeloid leukemia via multiple epigenetic actions. Experimental hematology 17 32007477
2002 Characterisation and developmental expression of mouse Plu-1, a homologue of a human nuclear protein (PLU-1) which is specifically up-regulated in breast cancer. Mechanisms of development 17 14516692
2023 Downregulated liver-elevated long intergenic noncoding RNA (LINC02428) is a tumor suppressor that blocks KDM5B/IGF2BP1 positive feedback loop in hepatocellular carcinoma. Cell death & disease 16 37137887
2022 H3K4 demethylase KDM5B regulates cancer cell identity and epigenetic plasticity. Oncogene 16 35440714
2022 KDM5B regulates the PTEN/PI3K/Akt pathway to increase sorafenib-resistance in hepatocellular carcinoma. Anti-cancer drugs 16 35946516

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