Affinage

KDM5B

Lysine-specific demethylase 5B · UniProt Q9UGL1

Length
1544 aa
Mass
175.7 kDa
Annotated
2026-04-28
100 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KDM5B is a JmjC-domain-containing, 2-oxoglutarate- and Fe(2+)-dependent histone demethylase that removes di- and trimethyl marks from histone H3 lysine 4 (H3K4me2/3), functioning as a transcriptional repressor at promoters and gene bodies to regulate cell proliferation, differentiation, DNA damage repair, and inflammatory signaling (PMID:17363312, PMID:27214403). KDM5B is recruited to chromatin through its PHD1 finger (which reads the H3K4me0 product), its PHD3 finger (which reads the H3K4me3 substrate), its ARID domain (which binds CG-rich DNA), and through interactions with MRG15 at intragenic H3K36me3 regions, where it prevents cryptic transcription and modulates RNA polymerase II elongation and alternative splicing (PMID:24412361, PMID:17709396, PMID:21448134, PMID:28402433). It operates within multiple repressive complexes—including LSD1/NuRD and SETDB1-containing complexes—and partners with transcription factors such as TFAP2C/Myc, ERα, Rb, and FOXP3, while its activity and stability are regulated by PARylation, SUMOylation, CDK1 phosphorylation, and ubiquitin-dependent turnover controlled by USP7, USP38, HSP90, and RNF4 (PMID:21937684, PMID:34671158, PMID:20832725, PMID:23970103, PMID:31776402, PMID:38287116, PMID:33240782). Beyond its catalytic role, KDM5B possesses demethylase-independent scaffolding functions—recruiting SETDB1 to silence endogenous retroelements and trigger innate immune sensing, and suppressing AML stemness genes through chromatin association rather than enzymatic activity (PMID:34671158, PMID:35217626).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2003 High

    Establishing that KDM5B acts as a transcriptional co-repressor by directly interacting with developmental transcription factors via a conserved VP motif resolved how this protein participates in gene silencing before its enzymatic activity was known.

    Evidence Yeast two-hybrid, reporter assays, and site-directed mutagenesis with BF-1 and PAX9

    PMID:12657635

    Open questions at the time
    • Enzymatic mechanism of repression not yet identified
    • Endogenous genomic targets of KDM5B-BF-1/PAX9 complexes not defined
  2. 2007 High

    Identification of KDM5B as a bona fide H3K4me3 demethylase established the core enzymatic activity and linked it directly to transcriptional repression of target genes including BRCA1, while characterization of ARID domain DNA binding and HDAC interactions defined its multi-modal chromatin engagement.

    Evidence In vitro demethylase assays, ChIP, siRNA knockdown, DNA binding assays, co-immunoprecipitation with domain mutagenesis across three independent studies

    PMID:17363312 PMID:17373667 PMID:17709396

    Open questions at the time
    • Structural basis of the catalytic domain not yet resolved
    • In vivo developmental roles not yet tested genetically
    • Genome-wide target landscape unknown
  3. 2010 High

    Discovery that PARP1-mediated PARylation inhibits KDM5B demethylase activity at target promoters revealed the first post-translational regulatory switch controlling KDM5B function, while identification of the TIEG1/KLF10 interaction linked KDM5B to TGF-β pathway repression.

    Evidence PARylation assays, ChIP, siRNA knockdown, chromatin fractionation; co-IP and reporter assays for TIEG1 interaction

    PMID:20832725 PMID:20863814

    Open questions at the time
    • Whether PARylation directly modifies KDM5B or acts through complex disruption not fully resolved
    • TIEG1 interaction validated only in single lab
  4. 2011 High

    Multiple studies established that KDM5B operates within the LSD1/NuRD complex for coordinate H3K4 demethylation, is recruited to gene bodies via MRG15 to prevent cryptic transcription and regulate elongation, localizes genome-wide to developmental gene promoters in ESCs where it is essential for differentiation but not self-renewal, and is displaced from promoters by FOXP3.

    Evidence Co-IP identifying LSD1/NuRD complex membership with xenograft validation; ChIP-seq with MRG15 co-IP and elongation assays; genome-wide ChIP-seq in ESCs with shRNA differentiation assays; ChIP showing FOXP3-mediated displacement

    PMID:21448134 PMID:21937684 PMID:21969366 PMID:22020125 PMID:22152480

    Open questions at the time
    • Structural basis of MRG15-KDM5B interaction not determined
    • How KDM5B distinguishes promoter vs intragenic targets mechanistically unclear
    • FOXP3 displacement mechanism not defined at atomic level
  5. 2012 High

    Identification of KDM5B as part of a TFAP2C/Myc ternary complex at the p21 promoter and its recruitment by Rb to cell cycle gene promoters during senescence connected KDM5B demethylase activity to cell cycle control through distinct transcription factor partnerships.

    Evidence Reciprocal co-IP with domain mapping, ChIP at p21 promoter; ChIP-seq and quantitative histone MS with Rb epistasis

    PMID:22371483 PMID:22615382

    Open questions at the time
    • Whether Rb directly contacts KDM5B or acts through intermediaries not fully resolved
    • Relative contributions of KDM5A vs KDM5B at Rb target genes unclear
  6. 2013 Medium

    SUMOylation at K242/K278 by hPC2 and subsequent RNF4-mediated ubiquitin-dependent degradation were identified as a second post-translational regulatory axis, while PRC2/SUZ12 interaction revealed co-occupancy at retinoic acid-responsive regulatory elements.

    Evidence Co-IP, site-directed mutagenesis, digital gene expression for SUMOylation; in vitro pull-down, ChIP, reporter assays for PRC2 interaction

    PMID:23970103 PMID:24619877

    Open questions at the time
    • SUMOylation studies from single lab; independent confirmation needed
    • Biphasic co-activator function with RARα requires further mechanistic dissection
  7. 2014 High

    Structural characterization of KDM5B PHD fingers—PHD1 binding H3K4me0 (product) and PHD3 binding H3K4me3 (substrate)—explained the product-feedback recruitment mechanism, while discovery of PARP1- and macroH2A1.1-dependent recruitment to DNA double-strand breaks extended KDM5B function to DNA damage repair.

    Evidence Histone peptide binding assays with domain mutagenesis and migration assays; laser micro-irradiation, live imaging, siRNA epistasis at DSB foci

    PMID:24412361 PMID:24778210

    Open questions at the time
    • Atomic-resolution structure of PHD1-H3 complex not yet available
    • Whether KDM5B demethylase activity is required at DSBs or only its scaffold function is unclear
    • Relative contributions to HR vs NHEJ not quantified
  8. 2015 High

    Target gene studies in endothelial cells (HOXA5), hepatocellular carcinoma (PTEN), and myogenic differentiation (RUNX2) demonstrated that KDM5B's promoter-specific H3K4me2/3 demethylation directly regulates diverse physiological programs including angiogenesis, AKT signaling, and lineage commitment, while SKP2/TRAF6-mediated K63-ubiquitination was shown to regulate KDM5B activity.

    Evidence ChIP with endothelial-specific conditional KO mice and retinal angiogenesis assay; ChIP with PTEN rescue and xenograft; ChIP with differentiation assays; co-IP and ubiquitination assays with tumor models

    PMID:25596733 PMID:25909289 PMID:26023081 PMID:26453309

    Open questions at the time
    • Whether K63-ubiquitination enhances demethylase activity directly or through chromatin recruitment not established
    • PTEN regulation validated in single lab
  9. 2016 High

    Crystal structures of the KDM5B catalytic core in complex with three inhibitor chemotypes revealed active-site architecture distinct from KDM4 and KDM6 families, providing the structural foundation for selective inhibitor development.

    Evidence X-ray crystallography with in vitro enzymatic and cellular H3K4me3 assays

    PMID:27214403

    Open questions at the time
    • Full-length KDM5B structure including PHD fingers and ARID domain not solved
    • How inhibitor binding relates to in vivo chromatin context unknown
  10. 2017 High

    Genome-wide GRO-seq and RNA-seq in ES cells established that KDM5B controls RNA polymerase II promoter occupancy, transcriptional elongation rates, and alternative splicing by confining H3K4me3 to promoters and preventing its spreading into gene bodies.

    Evidence ChIP-seq, GRO-seq, RNA-seq upon KDM5B knockdown in ES cells

    PMID:28402433

    Open questions at the time
    • Whether splicing regulation requires direct KDM5B interaction with splicing machinery or is purely epigenetic not determined
    • Contribution of individual PHD fingers to elongation regulation unknown
  11. 2018 Medium

    HSP90 was identified as a chaperone that stabilizes KDM5B by preventing ubiquitin-dependent degradation, linking protein quality control to KDM5B-mediated chemoresistance through H3K4 demethylation at DNA damage sites and XRCC1 recruitment.

    Evidence Mass spectrometry interactome, co-IP, ChIP, knockdown/overexpression with in vivo tumor models in cisplatin-resistant gastric cancer

    PMID:29989047

    Open questions at the time
    • Direct ubiquitin E3 ligase counteracted by HSP90 not identified in this study
    • Single-lab finding
  12. 2020 High

    Two studies revealed distinct regulatory inputs: CDK1 phosphorylation at S1456 attenuates KDM5B promoter occupancy at pluripotency genes with HEXIM1 mediating recruitment, while USP38 deubiquitinates H2BK120 to enable KDM5B recruitment and additionally stabilizes KDM5B protein, connecting cell cycle and inflammatory signaling to KDM5B regulation. KDM5B was also shown to promote prostate cancer via direct PIK3CA promoter binding and PI3K/AKT activation.

    Evidence Mass spectrometry with mutagenesis and ChIP for CDK1/HEXIM1; co-IP, ChIP, USP38 KO mice for inflammatory phenotype; ChIP with prostate-specific conditional KO and Pten epistasis in mice

    PMID:31776402 PMID:32868382 PMID:33240782

    Open questions at the time
    • Whether CDK1 phosphorylation affects KDM5B stability in addition to chromatin binding not tested
    • HEXIM1-KDM5B interaction mechanism not structurally defined
  13. 2021 High

    A landmark study demonstrated that KDM5B recruits SETDB1 to silence endogenous retroelements in a demethylase-independent manner; loss of this scaffold function derepresses retroelements, activating cytosolic nucleic acid sensing pathways and type-I interferon responses that enable anti-tumor immunity.

    Evidence Co-IP, CRISPR/siRNA depletion, catalytic-dead mutant, retroelement expression assays, immune functional assays in mouse melanoma models

    PMID:34671158

    Open questions at the time
    • Which domain of KDM5B mediates SETDB1 recruitment not mapped
    • Whether this pathway operates in all tumor types or is context-specific unknown
    • Contribution of specific retroelement families not resolved
  14. 2022 High

    Studies in AML and cardiac fibrosis revealed context-dependent functions: in AML, KDM5B suppresses stemness genes through scaffolding rather than demethylase activity, while in cardiac fibroblasts it promotes fibrosis by demethylating H3K4me2/3 at the ATF3 promoter to enhance TGF-β signaling.

    Evidence ChIP-seq, CUT&RUN, catalytic mutant in mouse AML models; ChIP with cardiac-specific KO and MI models

    PMID:35217626 PMID:36481938

    Open questions at the time
    • Structural basis for demethylase-independent chromatin association in AML not defined
    • Whether cardiac fibrosis role is direct or partly mediated through immune cell KDM5B not excluded
  15. 2023 High

    Genome-wide profiling in macrophages revealed selective KDM5B recruitment to the Nfkbia (IκBα) promoter where it erases H3K4me3 and reduces chromatin accessibility, amplifying NF-κB signaling; KDM5B deficiency protects against inflammatory injury, establishing KDM5B as a direct epigenetic amplifier of inflammatory NF-κB responses.

    Evidence ChIP-seq, ATAC-seq, KDM5B KO macrophages, in vivo inflammatory models

    PMID:36914768

    Open questions at the time
    • Whether KDM5B's pro-inflammatory role at Nfkbia conflicts with its anti-inflammatory role via USP38 pathway at Il6/Il23a is unresolved
    • Upstream signals selecting Nfkbia as a KDM5B target in macrophage activation unknown
  16. 2024 High

    USP7 was identified as a deubiquitinase that directly stabilizes KDM5B, which in turn represses ZBTB16 to upregulate TOP2A and confer cisplatin resistance, adding another ubiquitin-regulatory axis controlling KDM5B protein levels.

    Evidence Co-IP, ChIP, ubiquitination assays, siRNA/CRISPR, in vivo xenograft in nasopharyngeal carcinoma

    PMID:38287116

    Open questions at the time
    • Specific ubiquitin linkage type removed by USP7 not determined
    • Whether USP7 and USP38 act redundantly or in different contexts not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full-length structure of KDM5B integrating all reader and catalytic domains, the molecular determinants that switch KDM5B between demethylase-dependent and scaffold-only modes, how the opposing pro- and anti-inflammatory activities at different gene loci are reconciled, and whether PHD finger reading states create a processive demethylation mechanism on chromatin.
  • No full-length KDM5B structure available
  • Mechanism toggling enzymatic vs scaffold functions not defined
  • Locus-selective recruitment logic in immune cells unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0140110 transcription regulator activity 3 GO:0016491 oxidoreductase activity 2 GO:0042393 histone binding 2 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 4 GO:0000228 nuclear chromosome 3 GO:0005694 chromosome 2
Pathway
R-HSA-4839726 Chromatin organization 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 3 R-HSA-73894 DNA Repair 2
Partners
HDAC4HSP90LSD1MRG15SETDB1SUZ12USP38USP7
Complex memberships
LSD1/NuRD complexSETDB1-containing retroelement silencing complexTFAP2C/Myc co-repressor complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 PLU-1/KDM5B is a histone H3K4 demethylase that catalyzes removal of the trimethyl H3K4 modification; this demethylase activity is required for transcriptional repression of target genes including BRCA1 and is necessary for breast cancer cell proliferation. In vitro histone demethylase assay, siRNA knockdown with ChIP and gene expression readouts Molecular cell High 17363312
2007 KDM5B ARID domain selectively binds CG-rich DNA with a GCACA/C consensus motif found in metallothionein promoters; KDM5B directly occupies and represses the MT1H, MT1F, and MT1X promoters in vivo, reducing H3K4me3 levels at these loci. ChIP assay, DNA binding assays, microarray with adenoviral overexpression and RNAi knockdown Molecular and cellular biology High 17709396
2007 KDM5B interacts directly with class I and class IIa histone deacetylases (HDACs); two PHD domains of KDM5B mediate binding to a domain in the 5' region of HDAC4 overlapping the MEF2 binding region, and this interaction is required for full transcriptional repression activity. Co-immunoprecipitation, domain deletion/mutagenesis, cotransfection localization assays International journal of cancer High 17373667
2003 KDM5B (PLU-1) interacts with developmental transcription factors BF-1 and PAX9 via a conserved VP motif (Ala-X-Ala-Ala-X-Val-Pro-X4-Val-Pro-X8-Pro) and acts as a transcriptional co-repressor that enhances repression by these factors; mutation of the VP motif abolishes interaction and co-repression. Yeast two-hybrid, reporter repression assays, site-directed mutagenesis The Journal of biological chemistry High 12657635
2010 PARP-1 inhibits KDM5B activity through PARylation, which prevents KDM5B from demethylating H3K4me3 at promoters of PARP-1-regulated genes; depletion of PARP-1 allows KDM5B to demethylate H3K4me3, leading to transcriptional repression and chromatin compaction. ChIP, PARylation assays, siRNA knockdown, chromatin fractionation Molecular cell High 20832725
2011 KDM5B is a physical component of the LSD1/NuRD complex; KDM5B and LSD1 act sequentially and coordinately to demethylate H3K4, and together repress the CCL14 chemokine pathway, suppressing angiogenesis and metastasis in breast cancer cells. Co-immunoprecipitation, genome-wide transcriptional analysis, in vivo xenograft assays Cancer research High 21937684
2014 KDM5B PHD1 finger specifically binds unmodified histone H3 (H3K4me0, the demethylation product), while PHD3 finger preferentially binds the trimethylated substrate H3K4me3; PHD2 has no histone-binding activity. The PHD1–H3K4me0 interaction is essential for KDM5B-mediated inhibition of cell migration. Histone peptide binding assays, structural analysis, RNA-seq, Co-IP with NuRD complex, functional migration assay with PHD1 mutations Cell reports High 24412361
2016 Crystal structures of the catalytic core of human KDM5B (a 2-oxoglutarate- and Fe(2+)-dependent oxygenase) were solved in complex with three inhibitor chemotypes, revealing active site features distinct from KDM4 and KDM6 families and enabling rational inhibitor design. X-ray crystallography, in vitro enzymatic inhibition assays, cellular H3K4me3 elevation assays Nature chemical biology High 27214403
2011 KDM5B is recruited to intragenic H3K36me3 regions via interaction with the chromodomain protein MRG15; depletion of KDM5B or MRG15 increases intragenic H3K4me3 and cryptic intragenic transcription, and inhibits transcriptional elongation of KDM5B target genes. ChIP-seq, siRNA knockdown, RNA-seq, co-immunoprecipitation The EMBO journal High 21448134
2011 Jarid1b (KDM5B) genome-wide localizes predominantly to transcription start sites of developmental regulator genes (many co-bound by Polycomb); depletion of Jarid1b in ESCs causes global H3K4me3 increase and failure to silence lineage-inappropriate genes during neural differentiation, demonstrating KDM5B is dispensable for ESC self-renewal but essential for neural lineage differentiation. Genome-wide ChIP-seq (location analysis), shRNA knockdown, differentiation assays The EMBO journal High 22020125
2012 Jarid1b (KDM5B) and Jarid1a are recruited by the retinoblastoma tumor suppressor to demethylate H3K4 at cell cycle gene promoters, contributing to gene silencing in cellular senescence; Rb-depleted cells show loss of H3K4 demethylation at these loci. ChIP-seq, quantitative mass spectrometry (histone modifications), siRNA knockdown PNAS High 22615382
2014 KDM5B is recruited to DNA double-strand break (DSB) sites in a PARP1- and macroH2A1.1-dependent manner; KDM5B is required for efficient DSB repair and for recruitment of Ku70 (NHEJ) and BRCA1 (HR); KDM5B deficiency promotes spontaneous DNA damage and activates p53 signaling. Laser micro-irradiation/live imaging, siRNA knockdown, immunofluorescence at damage foci, cell sensitivity assays PNAS High 24778210
2013 KDM5B physically associates with PRC2 through direct interaction between KDM5B and the SUZ12 component; KDM5B and PRC2 co-occupy conserved cis-regulatory elements of retinoic acid (RA) responsive genes, and KDM5B functions as a co-activator for RA signaling through its JmjC domain interaction with RARα, exerting a biphasic effect on RA-induced gene activation. In vitro pull-down, ChIP, co-immunoprecipitation, transcription reporter assays, domain mutagenesis Journal of cellular biochemistry Medium 24619877
2013 KDM5B is SUMOylated at Lys242 and Lys278 by hPC2 SUMO E3 ligase; SUMOylation negatively regulates KDM5B chromatin occupancy, and SUMOylated KDM5B is targeted for proteasomal degradation by the E3 ubiquitin ligase RNF4. SUMOylation-deficient KDM5B shows increased repression of cell cycle and DNA repair gene expression. Co-immunoprecipitation, site-directed mutagenesis, digital gene expression, ChIP Epigenetics Medium 23970103
2015 SKP2 decreases K63-linked ubiquitination of KDM5B by the E3 ubiquitin ligase TRAF6, thereby decreasing KDM5B demethylase activity and increasing H3K4me3; Skp2 deficiency increases JARID1B ubiquitination, reduces H3K4me3, and induces senescence via accumulation of JARID1B in nucleoli. Co-immunoprecipitation, ubiquitination assays, in vitro/in vivo tumor models, mouse genetics Oncotarget Medium 25596733
2012 KDM5B forms a ternary complex with TFAP2C and Myc at the proximal CDKN1A (p21) promoter and acts as a corepressor dependent on TFAP2C and Myc; the complex demethylates H3K4me3 at the promoter to repress p21, requiring both the AP-2 binding site and KDM5B demethylase activity; all three factors are required for optimal repression. Co-immunoprecipitation, ChIP, reporter assays, domain mapping, cell cycle assays Molecular and cellular biology High 22371483
2011 FOXP3 displaces KDM5B (PLU-1) from target gene promoters near transcriptional start sites while simultaneously recruiting MOF; this coordinated pull-push mechanism increases H3K4me3 and H4K16 acetylation at FOXP3-activated genes. ChIP, RNAi silencing, reporter assays, immunoprecipitation Molecular cell Medium 22152480
2011 JARID1B directly occupies the let-7e promoter and removes the H3K4me3 mark, epigenetically repressing let-7e expression; repression of let-7e by JARID1B releases its target cyclin D1, promoting G1-to-S cell cycle progression in breast tumor cells. ChIP, RNAi knockdown, cell cycle FACS, luciferase and rescue assays The Journal of biological chemistry High 21969366
2010 KDM5B interacts with TIEG1/KLF10 through the repression domains of TIEG1 binding to the C-terminus of KDM5B; overexpression of KDM5B augments TIEG1-mediated repression of Smad7, an inhibitor of TGF-β signaling, while KDM5B knockdown increases Smad7 mRNA levels. Co-immunoprecipitation, domain mapping, reporter assays, siRNA knockdown Biochemical and biophysical research communications Medium 20863814
2015 KDM5B directly occupies and demethylates H3K4me2/3 at the HOXA5 promoter in endothelial cells, suppressing HOXA5 expression and maintaining angiogenic capacity; endothelial-specific Jarid1b knockout mice show attenuated retinal angiogenesis. ChIP, shRNA knockdown, pharmacological inhibition, endothelial-specific conditional knockout mice, microarray Arteriosclerosis, thrombosis, and vascular biology High 26023081
2015 KDM5B directly occupies the PTEN gene promoter and reduces H3K4me3, repressing PTEN transcription, thereby activating AKT signaling and promoting HCC metastasis. ChIP, overexpression/knockdown, PTEN rescue experiments, in vivo xenograft Oncotarget Medium 25909289
2015 KDM5B demethylase activity at the RUNX2 P1 promoter is required for repression of RUNX2 during myogenic differentiation; knockdown of KDM5B (but not UTX or NO66) prevents this repression and maintains H3K4me3 and H3K27ac marks at the Runx2 promoter. ChIP, siRNA knockdown, differentiation assays, promoter reporter assays The Journal of biological chemistry Medium 26453309
2014 KDM5B is required for GATA3 recruitment to the Foxa1 promoter to activate Foxa1 expression in mammary epithelial cells; KDM5B loss diminishes expression of FOXA1 and estrogen receptor α, impairing luminal lineage specification. ChIP, Jarid1b knockout mice, mammary gland phenotype analysis The Journal of biological chemistry Medium 24802759
2020 KDM5B directly binds the PIK3CA promoter to promote PI3K/AKT signaling; KDM5B knockout reduces P110α and PIP3 levels and decreases proliferation in prostate cancer cells; Pten/Kdm5b double-null mice show significantly delayed prostate cancer onset compared to Pten-null mice. ChIP, prostate epithelium-specific conditional knockout mice, in vitro proliferation assays, PI3K pathway biochemistry Cancer research High 32868382
2021 KDM5B recruits the H3K9 methyltransferase SETDB1 to repress endogenous retroelements (e.g., MMVL30) in a demethylase-independent manner; derepression activates cytosolic RNA- and DNA-sensing pathways and a type-I interferon response, enabling anti-tumor immune responses. Co-immunoprecipitation, CRISPR/siRNA depletion, retroelement expression assays, immune functional assays in mouse melanoma models Nature High 34671158
2020 USP38 deubiquitinates H2B at lysine 120 (H2BK120), and this is required for subsequent recruitment of KDM5B to promoters of pro-inflammatory cytokine genes (Il6, Il23a) during LPS stimulation; KDM5B then reduces H3K4me3 and inhibits NF-κB binding at these promoters. Additionally, USP38 directly binds KDM5B and protects it from proteasomal degradation. Co-immunoprecipitation, ChIP, knockdown, USP38 knockout mice with inflammatory phenotype, ubiquitination assays Advanced science High 33240782
2019 KDM5B is phosphorylated at Ser1456 by cyclin-dependent kinase 1 (CDK1); this phosphorylation attenuates KDM5B occupancy on promoters of pluripotency genes (SOX2, NANOG). HEXIM1 is required as a mediator for KDM5B recruitment to target gene promoters. Mass spectrometry, site-directed mutagenesis, ChIP, co-immunoprecipitation Scientific reports Medium 31776402
2018 HSP90 forms a complex with KDM5B and protects it from ubiquitin-dependent proteasomal degradation in cisplatin-resistant gastric cancer cells; HSP90 inhibitor 17-AAG induces KDM5B degradation; KDM5B demethylates H3K4 at DNA damage sites and facilitates recruitment of XRCC1 to promote chemoresistance. Mass spectrometry, co-immunoprecipitation, ChIP, knockdown/overexpression, in vivo tumor models International journal of biological sciences Medium 29989047
2024 The deubiquitinase USP7 binds KDM5B and stabilizes it by preventing its ubiquitin-mediated proteasomal degradation; KDM5B inhibits ZBTB16 expression by directly reducing H3K4me3 at the ZBTB16 promoter, which increases TOP2A expression and confers cisplatin resistance in nasopharyngeal carcinoma. Co-immunoprecipitation, ChIP, ubiquitination assays, siRNA/CRISPR knockdown, in vivo xenograft models Cell death and differentiation High 38287116
2023 KDM5B is selectively recruited to the Nfkbia (IκBα) promoter in activated macrophages where it erases H3K4me3 and reduces chromatin accessibility, suppressing IκBα expression and thereby amplifying NF-κB signaling and pro-inflammatory cytokine production; KDM5B deficiency or inhibitor treatment protects mice from inflammatory injury. Genome-wide ChIP-seq, ATAC-seq, KDM5B knockout macrophages, in vivo inflammatory models Cell death and differentiation High 36914768
2022 KDM5B binds the promoter of ATF3 (an antifibrotic transcription factor) and inhibits ATF3 expression by demethylating H3K4me2/3, leading to enhanced TGF-β signaling and excessive profibrotic gene expression; KDM5B deficiency or inhibition ameliorates cardiac fibrosis and dysfunction following myocardial infarction. ChIP, KDM5B knockout mice with cardiac injury models, cardiac fibroblast assays, pharmacological inhibition Experimental & molecular medicine High 36481938
2017 KDM5B regulates RNA polymerase II promoter occupancy and both transcriptional initiation/elongation rates and alternative splicing in ES cells; depletion of KDM5B leads to spreading of H3K4me3 from promoters into gene bodies, which alters RNAPII elongation and RNA splicing. KDM5B is enriched near alternatively spliced exons. ChIP-seq, GRO-seq, RNA-seq, KDM5B knockdown in ES cells Nucleic acids research High 28402433
2022 In AML, KDM5B is a direct transcriptional target repressed by PRC2 (EZH2). Ectopic KDM5B expression suppresses AML growth and directly binds and represses AML stemness genes; the anti-AML effect depends on KDM5B's chromatin association/scaffold functions rather than its demethylase activity. ChIP-seq, CUT&RUN, RNA-seq, ectopic expression, genetic knockdown in mouse AML models PNAS High 35217626
2008 KDM5B demethylates H3K4 at promoters of Egr1, p27(KIP1), and BMI1, repressing their expression; overexpression blocks terminal differentiation of ESCs by maintaining cyclins and preventing upregulation of lineage markers; KDM5B also directly regulates mTcf3/hTcf7L1 upstream of Nanog expression. Demethylation assays at specific promoters, ChIP, differentiation assays (neural and embryoid body), overexpression Molecular and cellular biology Medium 18591252
2015 Ikaros represses KDM5B transcription in B-ALL through an Ikaros-HDAC1 complex that binds the KDM5B upstream regulatory element; this repression is impaired by casein kinase 2 (CK2) phosphorylation of Ikaros. CK2 inhibition restores Ikaros-HDAC1 complex binding, increases H3K27me3 and decreases H3K9ac at the KDM5B promoter. ChIP, co-immunoprecipitation, siRNA/inhibitor treatments, B-ALL cell proliferation assays The Journal of biological chemistry Medium 26655717
2011 JARID1B interaction with estrogen receptor α (ERα) was demonstrated biochemically; downregulation of JARID1B in MCF-7 cells dramatically decreased estrogen-stimulated tumor growth in vivo, and the ARID domain of JARID1B is required for normal mammary gland development. Co-immunoprecipitation, shRNAi knockdown, in vivo xenograft/tumor growth, ARID domain deletion mouse strain International journal of oncology Medium 21369698
2025 EBV EBNA1 interacts with transcription factor CEBPB to upregulate KDM5B; KDM5B directly binds the PLK2 gene promoter, demethylates H3K4 to repress PLK2, and activates the PI3K/AKT/mTOR signaling pathway promoting malignant progression in EBV-associated epithelial cancers. ChIP, co-immunoprecipitation, functional assays, patient-derived xenograft models, KDM5B inhibitor treatment Signal transduction and targeted therapy Medium 40059116

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 Overcoming intrinsic multidrug resistance in melanoma by blocking the mitochondrial respiratory chain of slow-cycling JARID1B(high) cells. Cancer cell 568 23764003
2007 PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation. Molecular cell 391 17363312
2010 PARP-1 regulates chromatin structure and transcription through a KDM5B-dependent pathway. Molecular cell 271 20832725
2021 KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements. Nature 212 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
2010 Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway. Molecular cancer 174 20226085
2014 JARID1B is a luminal lineage-driving oncogene in breast cancer. Cancer cell 162 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 156 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 129 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 119 24778210
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 104 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 90 30448242
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
2007 Breast cancer associated transcriptional repressor PLU-1/JARID1B interacts directly with histone deacetylases. International journal of cancer 79 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 78 12657635
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 70 26083387
2013 KDM5B histone demethylase controls epithelial-mesenchymal transition of cancer cells by regulating the expression of the microRNA-200 family. Cell cycle (Georgetown, Tex.) 70 23759590
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
2015 JARID1B promotes metastasis and epithelial-mesenchymal transition via PTEN/AKT signaling in hepatocellular carcinoma cells. Oncotarget 66 25909289
2008 RBP2-H1/JARID1B is a transcriptional regulator with a tumor suppressive potential in melanoma cells. International journal of cancer 65 17973255
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
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 53 26184998
2015 JARID1B Expression Plays a Critical Role in Chemoresistance and Stem Cell-Like Phenotype of Neuroblastoma Cells. PloS one 52 25951238
2020 USP38 Couples Histone Ubiquitination and Methylation via KDM5B to Resolve Inflammation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 50 33240782
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
2013 Androgen receptor activation by polychlorinated biphenyls: epigenetic effects mediated by the histone demethylase Jarid1b. Epigenetics 47 23907094
2018 KDM5B Promotes Drug Resistance by Regulating Melanoma-Propagating Cell Subpopulations. Molecular cancer therapeutics 46 30523048
2017 H3K4 demethylase KDM5B regulates global dynamics of transcription elongation and alternative splicing in embryonic stem cells. Nucleic acids research 46 28402433
2016 JARID1B Enables Transit between Distinct States of the Stem-like Cell Population in Oral Cancers. Cancer research 46 27488530
2019 NEK2 promotes proliferation, migration and tumor growth of gastric cancer cells via regulating KDM5B/H3K4me3. American journal of cancer research 45 31815040
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
2018 Lysine demethylase 5B (KDM5B): A potential anti-cancer drug target. European journal of medicinal chemistry 41 30343192
2015 Impairment of preimplantation porcine embryo development by histone demethylase KDM5B knockdown through disturbance of bivalent H3K4me3-H3K27me3 modifications. Biology of reproduction 40 25609834
2023 Histone demethylase KDM5B licenses macrophage-mediated inflammatory responses by repressing Nfkbia transcription. Cell death and differentiation 37 36914768
2020 Histone Demethylase KDM5B as a Therapeutic Target for Cancer Therapy. Cancers 37 32751840
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
2024 Deubiquitinase USP7 stabilizes KDM5B and promotes tumor progression and cisplatin resistance in nasopharyngeal carcinoma through the ZBTB16/TOP2A axis. Cell death and differentiation 36 38287116
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
2016 miR-194 inhibits gastric cancer cell proliferation and tumorigenesis by targeting KDM5B. European review for medical and pharmacological sciences 33 27874950
2022 Loss of KDM5B ameliorates pathological cardiac fibrosis and dysfunction by epigenetically enhancing ATF3 expression. Experimental & molecular medicine 32 36481938
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
2022 A PRC2-Kdm5b axis sustains tumorigenicity of acute myeloid leukemia. Proceedings of the National Academy of Sciences of the United States of America 31 35217626
2013 SUMOylation negatively modulates target gene occupancy of the KDM5B, a histone lysine demethylase. Epigenetics 31 23970103
2019 JARID1B expression and its function in DNA damage repair are tightly regulated by miRNAs in breast cancer. Cancer science 30 30588710
2019 Targeting the H3K4 Demethylase KDM5B Reprograms the Metabolome and Phenotype of Melanoma Cells. The Journal of investigative dermatology 30 31229500
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
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 29 25877751
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
2022 KDM5B promotes tumorigenesis of Ewing sarcoma via FBXW7/CCNE1 axis. Cell death & disease 26 35428764
2019 Investigation of the potential theranostic role of KDM5B/miR-29c signaling axis in paclitaxel resistant endometrial carcinoma. Gene 26 30658067
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
2018 Investigation of ovatodiolide, a macrocyclic diterpenoid, as a potential inhibitor of oral cancer stem-like cells properties via the inhibition of the JAK2/STAT3/JARID1B signal circuit. Phytomedicine : international journal of phytotherapy and phytopharmacology 25 30097127
2014 Coordinated regulation of retinoic acid signaling pathway by KDM5B and polycomb repressive complex 2. Journal of cellular biochemistry 25 24619877
2022 Drawing a line between histone demethylase KDM5A and KDM5B: their roles in development and tumorigenesis. Experimental & molecular medicine 24 36509829
2019 The Lysine Demethylase KDM5B Regulates Islet Function and Glucose Homeostasis. Journal of diabetes research 24 31467927
2020 JARID1B promotes colorectal cancer proliferation and Wnt/β-catenin signaling via decreasing CDX2 level. Cell communication and signaling : CCS 23 33109187
2017 Hepatitis B virus X protein induces hepatic stem cell-like features in hepatocellular carcinoma by activating KDM5B. World journal of gastroenterology 22 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 22 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
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
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
2018 KDM5B decommissions the H3K4 methylation landscape of self-renewal genes during trophoblast stem cell differentiation. Biology open 18 29748167
2016 Overexpression of JARID1B promotes differentiation via SHIP1/AKT signaling in human hypopharyngeal squamous cell carcinoma. Cell death & disease 18 27584795
2022 Alcohol-associated fibrosis in females is mediated by female-specific activation of lysine demethylases KDM5B and KDM5C. Hepatology communications 17 35468265
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 KDM5B regulates the PTEN/PI3K/Akt pathway to increase sorafenib-resistance in hepatocellular carcinoma. Anti-cancer drugs 16 35946516
2025 Epstein-Barr virus hijacks histone demethylase machinery to drive epithelial malignancy progression through KDM5B upregulation. Signal transduction and targeted therapy 15 40059116
2022 H3K4 demethylase KDM5B regulates cancer cell identity and epigenetic plasticity. Oncogene 15 35440714
2021 MiR-374b-5p inhibits KDM5B-induced epithelial-mesenchymal transition in pancreatic cancer. American journal of cancer research 15 34522457