Affinage

ARID3B

AT-rich interactive domain-containing protein 3B · UniProt Q8IVW6

Length
561 aa
Mass
60.6 kDa
Annotated
2026-06-09
23 papers in source corpus 18 papers cited in narrative 18 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ARID3B is a nuclear ARID-family DNA-binding transcription factor that controls programs of proliferation, stemness, and developmental cell movement by binding A/T-rich ARID3 recognition sites in target promoters and enhancers (PMID:26121572, PMID:33649863). It functions cooperatively with its paralog ARID3A and the histone demethylase KDM4C as a triprotein complex that is recruited to chromatin, where KDM4C reduces repressive H3K9me3 to activate transcription of stemness and proliferation genes including HMGA1, c-MYC, VEGF-A, and WNT1 (PMID:26776511, PMID:31415216); nuclear assembly of this complex depends on importin-9-mediated import of ARID3A, and the whole module is held in check post-transcriptionally by let-7 miRNAs (PMID:26776511). ARID3B directly occupies and activates E2F-target cell-cycle promoters (Cdc2, cyclin E1, p107) to drive cell-cycle progression (PMID:33649863), and also binds and activates pro-apoptotic p53 targets (PUMA, PIG3) and TNFα-pathway genes, so that ARID3B overexpression can induce apoptosis following DNA damage (PMID:22860069, PMID:26519881). Beyond transcription, ARID3B undergoes liquid-liquid phase separation to form granules that recruit SMAD2/3 coactivators and establish enhancer activity (PMID:41032419), and its nuclear confinement versus cytoplasmic/membrane distribution is set by phosphorylation at Serine 89 (PMID:41972703). In vivo, ARID3B is required for second-heart-field progenitor deployment and myocardial differentiation (PMID:25336743), apical ectodermal ridge morphogenesis through control of actin cytoskeleton and cell motility (PMID:21307092), and common lymphoid progenitor and B-cell development (PMID:27537840); it promotes ovarian and neuroblastoma tumorigenicity and cancer stem-cell expansion (PMID:16951138, PMID:25327563), restrains the KSHV lytic cycle by binding the viral origin of lytic replication (PMID:27512077), and in CD8+ T cells suppresses antitumor activity by downregulating Runx3 (PMID:42140952).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2006 Medium

    Established that ARID3B has intrinsic oncogenic potential, framing it as more than a passive DNA-binding factor.

    Evidence Retroviral ARID3B transduction immortalizing MEFs and conferring malignancy with MYCN, plus knockdown in neuroblastoma lines

    PMID:16951138

    Open questions at the time
    • No direct target genes identified to explain immortalization
    • Mechanism of cooperation with MYCN unresolved
  2. 2011 Medium

    Showed ARID3B is required for a morphogenetic cell-movement program, extending its role beyond proliferation to tissue patterning.

    Evidence In situ hybridization, dominant-negative interference and DiI labeling in chick/mouse AER, with cytoskeleton and migration assays

    PMID:21307092

    Open questions at the time
    • Transcriptional targets controlling actin/motility not defined
    • Link between DNA-binding activity and cytoskeletal phenotype unclear
  3. 2012 Medium

    Defined isoform- and localization-dependent function and an upstream signaling input, distinguishing nuclear transcriptional activity from cytosolic forms.

    Evidence Subcellular fractionation, isoform overexpression and apoptosis/transcriptional readouts in ovarian cancer cells; EGFR-PEA3 activation of ARID3B

    PMID:22860069

    Open questions at the time
    • Function of the short cytosolic isoform unknown
    • How localization is dynamically controlled not addressed at this stage
  4. 2014 Medium

    Connected ARID3B to in vivo developmental progenitor deployment and to cancer stem-cell programs, separating its functions across contexts.

    Evidence Conditional KO mouse cardiac analysis with DiI labeling and microarray; ovarian cancer xenografts with stem-cell marker and drug-resistance readouts

    PMID:25327563 PMID:25336743

    Open questions at the time
    • Direct vs indirect regulation of Bhlhb2/Lims2 and stem-cell genes not resolved
    • Whether cardiac and stem-cell roles share a common molecular mechanism unknown
  5. 2015 Medium

    Identified direct genomic targets and a defined binding motif, establishing ARID3B as a sequence-specific activator of both growth/adhesion and pro-apoptotic p53 programs.

    Evidence ChIP-chip with motif analysis and ChIP-qPCR validation (EGFR enhancer, Wnt5A/FZD5), plus in vitro and in vivo binding to p53 targets with knockdown

    PMID:26121572 PMID:26519881

    Open questions at the time
    • Determinants of activator-versus-context dependence not defined
    • Cofactors required at p53 target promoters not identified here
  6. 2016 High

    Resolved how the active nuclear complex is assembled and regulated, defining the let-7 → importin-9 → ARID3A/ARID3B/KDM4C axis controlling stemness gene transcription.

    Evidence Reporter, reciprocal Co-IP, ChIP, knockdown/overexpression in cancer lines establishing complex assembly and H3K9me3 demethylation

    PMID:26776511

    Open questions at the time
    • Which gene loci require KDM4C demethylation in each tissue not mapped
    • Stoichiometry and order of complex assembly not determined
  7. 2016 Medium

    Defined lineage-specific developmental requirements and an antiviral restriction role, broadening the functional scope of ARID3B.

    Evidence Bone-marrow conditional KO with flow cytometry of lymphoid lineages; SILAC proteomics, ChIP and DNA-affinity assays on KSHV oriLyt with gain/loss-of-function reactivation readouts

    PMID:27512077 PMID:27537840

    Open questions at the time
    • B-cell-stage transcriptional targets of ARID3B unknown
    • How ARID3B binding to oriLyt mechanistically blocks lytic replication unresolved
  8. 2019 High

    Generalized the ARID3A/ARID3B/KDM4C triprotein complex to a non-cancer (trophoblast) context with defined promoter targets, supporting a conserved proliferative module.

    Evidence Reciprocal Co-IP, ChIP and CRISPR/siRNA knockout with RT-qPCR on HMGA1, c-MYC, VEGF-A, WNT1 in trophoblast cells

    PMID:31415216

    Open questions at the time
    • Tissue-specific recruitment signals not defined
    • Whether the same complex operates at all listed targets simultaneously unknown
  9. 2021 Medium

    Demonstrated direct ARID3B control of E2F-target cell-cycle promoters via mapped binding sites, mechanistically linking ARID3B to cell-cycle progression.

    Evidence ChIP in living cells, promoter-reporter assays with binding-site mutagenesis, knockdown/overexpression and cell-cycle analysis in NHDFs and T98G cells

    PMID:33649863

    Open questions at the time
    • Cooperativity with E2F1 at the molecular level not detailed
    • How the same factor balances proliferation versus death outputs unresolved
  10. 2025 Medium

    Revealed liquid-liquid phase separation as a biophysical mechanism by which ARID3B recruits SMAD2/3 coactivators to establish enhancer activity, adding a condensate-based layer to its transcriptional function.

    Evidence In vitro and in vivo LLPS assays, Co-IP for SMAD2/3, ChIP for enhancer activity, and zebrafish LLPS-disruption rescue of craniofacial phenotypes

    PMID:41032419

    Open questions at the time
    • Which ARID3B sequences drive condensation not defined
    • Relationship between LLPS and the ARID3A/KDM4C complex unknown
  11. 2026 Medium

    Identified Serine 89 phosphorylation as the switch governing nuclear retention and transcriptional output, and defined a RUNX3-dependent immunosuppressive role in CD8+ T cells.

    Evidence Phospho-mimetic/dead mutagenesis with ChIP and fractionation; in vivo CRISPR screen with Arid3b/Runx3 double-KO epistasis in a colorectal tumor model

    PMID:41972703 PMID:42140952

    Open questions at the time
    • Kinase responsible for S89 phosphorylation unidentified
    • Whether ARID3B represses Runx3 directly or indirectly unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ARID3B integrates its phosphorylation switch, phase separation, and ARID3A/KDM4C complex assembly into a single context-dependent regulatory logic remains unresolved.
  • Upstream kinase and signaling inputs to S89 not mapped
  • Determinants selecting proliferative versus pro-apoptotic target programs unknown
  • Structural basis of complex assembly and condensate formation not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 6 GO:0140110 transcription regulator activity 5 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-1640170 Cell Cycle 1 R-HSA-4839726 Chromatin organization 1
Partners
ARID3AIPO9KDM4CSMAD2SMAD3
Complex memberships
ARID3A/ARID3B/KDM4C triprotein complex

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 Let-7 miRNAs directly repress expression of ARID3B, ARID3A, and importin-9. In the absence of let-7, importin-9 facilitates nuclear import of ARID3A, which then forms a complex with ARID3B. The nuclear ARID3B complex recruits histone demethylase KDM4C to reduce H3K9me3 and promotes transcription of stemness factors. Reporter assays, co-immunoprecipitation, chromatin immunoprecipitation, siRNA knockdown, overexpression in cancer cell lines Cell reports High 26776511
2019 In human trophoblast cells, ARID3A, ARID3B, and KDM4C form a triprotein complex (ARID3B-complex) that binds promoter regions of HMGA1, c-MYC, VEGF-A, and WNT1 to activate their transcription. ARID3B knockout disrupts the complex and decreases expression of these target genes. Co-immunoprecipitation, chromatin immunoprecipitation, CRISPR/siRNA knockdown, LIN28A/B double-knockout and double-knockin cell lines, RT-qPCR FASEB journal High 31415216
2015 ARID3B binds directly to target gene sequences (identified binding motif similar to ARID3A) including an EGFR enhancer and the Wnt5A/FZD5 promoter, and increases their mRNA expression. ARID3B-increased adhesion to collagen IV requires FZD5. Chromatin immunoprecipitation followed by microarray (ChIP-chip), ChIP-qPCR, motif analysis, overexpression and knockdown in ovarian cancer cell lines, adhesion assays PloS one Medium 26121572
2012 ARID3B full-length isoform (ARID3B Fl) is predominantly nuclear but also present at plasma membrane and cytosol. A novel short splice form (ARID3B Sh) accumulates in cytosol and membrane when overexpressed. ARID3B Fl overexpression induces TNFα-mediated apoptosis by upregulating pro-apoptotic BIM and genes including TNFα, TRAIL, TRADD, TNF-R2, Caspase 10, and Caspase 7; ARID3B Sh does not induce apoptosis or these genes. ARID3B is transcriptionally activated by EGFR signaling through the PEA3 transcription factor. Subcellular fractionation, Western blotting, RT-qPCR, overexpression of isoforms in ovarian cancer cells, cell viability assays PloS one Medium 22860069
2015 ARID3B and ARID3A bind to putative ARID3-binding sites in p53 target genes (PUMA, PIG3, p53) both in vitro and in vivo. ARID3B silencing (more than ARID3A) blocks transcriptional activation of pro-apoptotic p53 target genes and blocks apoptosis following DNA damage. Only ARID3B overexpression (not ARID3A) induced apoptosis. In vitro DNA binding assays, chromatin immunoprecipitation, siRNA knockdown, overexpression, DNA damage assays in cancer cell lines Biochemical and biophysical research communications Medium 26519881
2006 ARID3B by itself can immortalize mouse embryonic fibroblasts (MEFs) in vitro, and confers malignancy to MEFs when combined with MYCN. siRNA/antisense knockdown of ARID3B suppresses in vitro growth of neuroblastoma cell lines. Retroviral transduction into MEFs, tumor growth assay in nude mice, antisense and siRNA knockdown of endogenous ARID3B in neuroblastoma lines Cancer research Medium 16951138
2011 Arid3b is expressed in the apical ectodermal ridge (AER) in mouse and chick embryos. Interference with Arid3b activity leads to aberrant AER development without altering cell numbers or major signaling gene expression. Cells deficient in Arid3b show abnormal actin cytoskeleton distribution and decreased motility in vitro, and pre-AER cell movements and their contribution to the AER are defective in vivo. In situ hybridization, dominant-negative/siRNA interference in chick embryos, DiI cell labeling in vivo, phalloidin staining, in vitro migration assays Development (Cambridge, England) Medium 21307092
2014 Arid3b is expressed in myocardium and second heart field progenitors. Arid3b-deficient mouse embryos show cardiac defects including shortening of poles, absent myocardial differentiation, and altered atrioventricular canal patterning with loss of epithelial-to-mesenchymal transition. DiI labeling shows defective second heart field cell addition to the heart. Arid3b regulates Bhlhb2 (cardiomyocyte differentiation regulator) and Lims2 (cell migration gene). Conditional knockout mouse model, DiI cell labeling, RNA microarray, histology, immunofluorescence Development (Cambridge, England) Medium 25336743
2016 Conditional bone marrow-specific deletion of Arid3b decreases common lymphoid progenitors (CLPs) and downstream B cell populations while T cell and myeloid lineages are unchanged; HSC populations are unperturbed (contrasting with Arid3a loss). Conditional knockout mouse model, flow cytometry of bone marrow populations PloS one Medium 27537840
2014 Overexpression of ARID3B in ovarian cancer cell lines increases tumor burden in nude mice and induces expression of cancer stem cell genes (CD44, LGR5, CD133/PROM1, Notch2) and expands the CD133+ cell population, accompanied by enhanced paclitaxel resistance. Stable overexpression, intraperitoneal xenograft in nude mice, flow cytometry for CD133, drug resistance assay Oncotarget Medium 25327563
2021 ARID3B directly binds to putative ARID3-binding sites within E2F target gene promoters (Cdc2, cyclin E1, p107) in living cells. ARID3B knockdown blocks transcription of these E2F targets. ARID3B overexpression activates cyclin E1 transcription and induces cell death with E2F1 assistance. Both ARID3B and ARID3A knockdown attenuate cell cycle progression. Mutation of ARID3B binding sites reduced Cdc2 promoter activity. ChIP in living cells, promoter-reporter assays with binding-site mutagenesis, siRNA knockdown, overexpression in NHDFs and T98G cells, cell cycle analysis International journal of oncology Medium 33649863
2012 miR-125b directly targets ARID3B in breast cancer cells, and silencing of ARID3B phenocopies miR-125b overexpression by decreasing cell migration in MCF7 cells. miRNA overexpression, siRNA knockdown of ARID3B, wound closure and transwell migration assays, phalloidin staining Cell structure and function Low 22307404
2016 KSHV lytic switch protein RTA enhances ARID3B expression; upon lytic reactivation ARID3B relocalizes to viral replication compartments. ARID3B binds A/T-rich elements in the KSHV origin of lytic replication (oriLyt) in a lytic cycle-dependent manner. siRNA knockdown of ARID3B enhances lytic reactivation, while ARID3B overexpression inhibits it, indicating ARID3B negatively regulates the KSHV lytic cycle. SILAC quantitative proteomics, siRNA knockdown, overexpression, DNA affinity assays, chromatin immunoprecipitation, doxycycline-inducible RTA cell line Journal of virology Medium 27512077
2026 Phosphorylation at Serine 89 of ARID3B controls its subcellular localization: phospho-mimetic S89D confines ARID3B to the nucleus, while phospho-dead S89A allows distribution to cytoplasm and membrane. Chromatin immunoprecipitation confirms direct gene regulation is enhanced in WT and S89D compared to S89A. S89D mirrors WT ARID3B in regulating transcriptional programs; S89A diverges. Site-directed mutagenesis, phospho-specific antibody generation, subcellular fractionation/immunofluorescence, chromatin immunoprecipitation, transcriptional reporter assays in ovarian cancer and glioblastoma cells Cells Medium 41972703
2026 Genetic ablation of Arid3b in CD8+ T cells enhances their intratumoral accumulation and antitumor activity. Mechanistically, Arid3b deficiency upregulates Runx3, driving a tissue-resident memory-like phenotype and effector function. Deletion of Runx3 abrogates the benefits of Arid3b deficiency, indicating a RUNX3-dependent mechanism. In vivo CRISPR/Cas9 screen, genetic deletion in CD8+ T cells, double knockout (Arid3b/Runx3), tumor infiltrating lymphocyte analysis in murine CMT93 colorectal cancer model Nature communications Medium 42140952
2025 ARID3B undergoes liquid-liquid phase separation (LLPS) both in vivo and in vitro, forming granules that recruit coactivators SMAD2/3 and establish enhancer activity. Disrupting ARID3B LLPS in zebrafish rescued migration, apoptosis, and morphological phenotypes associated with cleft lip/palate. LLPS assay in vitro and in vivo, co-immunoprecipitation for SMAD2/3, ChIP for enhancer activity, zebrafish morpholino/LLPS disruption rescue experiments Cell reports Medium 41032419
2020 ARID3A and ARID3B in ovarian cancer cells regulate nearly identical gene sets including Twist, MYCN, MMP2, GLI2, TIMP3, and WNT5B. ARID3A and ARID3B also induce expression of each other, providing evidence of transcriptional cooperativity. Stable transduction with ARID3A-GFP, ARID3B-RFP, or both, followed by RNA-sequencing in ovarian cancer cells Gene Low 32061921
2023 ARID3B and ARID3A overexpression markedly increases MALAT1 and NORAD lncRNA expression in non-small cell lung cancer cells, indicating direct transcriptional regulatory control. Overexpression of ARID3A and ARID3B in NSCLC cell lines with reporter/expression assays Pathology, research and practice Low 37977034

Source papers

Stage 0 corpus · 23 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 The Role of LIN28-let-7-ARID3B Pathway in Placental Development. International journal of molecular sciences 51 32455665
2016 let-7 Modulates Chromatin Configuration and Target Gene Repression through Regulation of the ARID3B Complex. Cell reports 43 26776511
2012 miR-125b targets ARID3B in breast cancer cells. Cell structure and function 40 22307404
2006 ARID3B induces malignant transformation of mouse embryonic fibroblasts and is strongly associated with malignant neuroblastoma. Cancer research 38 16951138
2012 Epigenetic regulation of the neuroblastoma genes, Arid3b and Mycn. Oncogene 32 22751132
2011 Apical ectodermal ridge morphogenesis in limb development is controlled by Arid3b-mediated regulation of cell movements. Development (Cambridge, England) 31 21307092
2015 ARID3B Directly Regulates Ovarian Cancer Promoting Genes. PloS one 30 26121572
2020 ARID3A and ARID3B induce stem promoting pathways in ovarian cancer cells. Gene 27 32061921
2014 ARID3B increases ovarian tumor burden and is associated with a cancer stem cell gene signature. Oncotarget 23 25327563
2014 Differential expression of ARID3B in normal adult tissue and carcinomas. Gene 20 24704276
2019 LIN28-let-7 axis regulates genes in immortalized human trophoblast cells by targeting the ARID3B-complex. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17 31415216
2012 ARID3B induces tumor necrosis factor alpha mediated apoptosis while a novel ARID3B splice form does not induce cell death. PloS one 16 22860069
2021 Distinct and overlapping roles of ARID3A and ARID3B in regulating E2F‑dependent transcription via direct binding to E2F target genes. International journal of oncology 13 33649863
2014 Arid3b is essential for second heart field cell deployment and heart patterning. Development (Cambridge, England) 13 25336743
2016 Arid3b Is Critical for B Lymphocyte Development. PloS one 10 27537840
2016 ARID3B: a Novel Regulator of the Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycle. Journal of virology 8 27512077
2015 Critical role of ARID3B in the expression of pro-apoptotic p53-target genes and apoptosis. Biochemical and biophysical research communications 8 26519881
2014 ARID3B expression in primary breast cancers and breast cancer-derived cell lines. Cellular oncology (Dordrecht, Netherlands) 5 25120063
2023 ARID3A and ARID3B exert direct regulatory control over the long non-coding RNAs (lncRNAs) MALAT1 and NORAD within the context of non-small cell lung cancer (NSCLC). Pathology, research and practice 2 37977034
2026 Serine 89 Phosphorylation Controls Nuclear Localization and Transcriptional Activity of ARID3B. Cells 0 41972703
2026 Arid3b suppresses CD8 + T cell infiltration and function in microsatellite-stable colorectal cancer via Runx3. Nature communications 0 42140952
2025 Genetic regulation of ARID3B confers cleft lip with/without cleft palate susceptibility through LLPS-mediated transcriptional program. Cell reports 0 41032419
2025 mmu_circ_0000684/hsa_circ_0067098 mediates renal tubular epithelial cells apoptosis to ischemia-reperfusion-induced acute kidney injury by targeting the mmu_miR_671-5p/ARID3B axis. Archives of biochemistry and biophysics 0 41320129

Missed literature

Know a paper Affinage missed for ARID3B? Flag it for the maintainers and the community.

No submissions yet.