Affinage

ING4

Inhibitor of growth protein 4 · UniProt Q9UNL4

Length
249 aa
Mass
28.5 kDa
Annotated
2026-06-10
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ING4 is a chromatin-reading tumor suppressor that couples recognition of the H3K4me3 active-promoter mark to histone acetyltransferase activity and to the control of multiple transcriptional programs governing growth, apoptosis, angiogenesis, and differentiation (PMID:19187765, PMID:17157298). It functions as a native subunit of the HBO1 (KAT7) histone acetyltransferase complex, where its PHD finger specifically binds H3K4me3 to augment HBO1-driven H3 acetylation at target promoters, an interaction required for ING4-dependent apoptosis after genotoxic stress and for suppression of anchorage-independent growth (PMID:19187765); ING4 and the paralog ING5 are similarly essential for H3K14 and H3K23 acetylation by KAT6A/KAT6B/KAT7 complexes during epicardial lineage development (PMID:38446206). ING4 homodimerizes through an N-terminal antiparallel coiled-coil, presenting two independent H3K4me3-binding PHD fingers for bivalent chromatin recognition, and disruption of dimerization abolishes its pro-apoptotic activity (PMID:20053357, PMID:22334692). Beyond the acetyltransferase complex, ING4 enhances p53 acetylation and p53-dependent p21 induction and apoptosis through an interaction requiring its NLS region (PMID:12750254, PMID:15882981), and directly binds NF-κB p65/RelA to repress NF-κB target genes at the chromatin level by lowering p300 recruitment, histone acetylation and H3K4me3 while promoting HDAC-1 recruitment, thereby restraining tumor angiogenesis (PMID:15029197, PMID:18779315). It additionally represses HIF transcriptional activity via association with HIF prolyl hydroxylases independently of HIF stability (PMID:15897452, PMID:17848618), represses MYC at the translational level by binding AUF1 on MYC mRNA (PMID:23603392), and drives rRNA transcription in the nucleolus through PHD-dependent localization to active rDNA promoters (PMID:31754246). ING4 abundance is controlled by CK2-mediated phosphorylation at Ser-150 that licenses SCF(JFK)-mediated ubiquitination and proteasomal degradation (PMID:25792601, PMID:37870169), and its p53-activating function is further modulated by PAD4-mediated citrullination of the NLS, which disrupts p53 binding (PMID:21454715).

Mechanistic history

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

    Established ING4 as a p53 cofactor, answering whether it acts through a defined transcriptional partner to enforce growth arrest and apoptosis.

    Evidence Co-IP with p300 and p53, p21/WAF1 reporter, and apoptosis/colony assays

    PMID:12750254

    Open questions at the time
    • Did not map the ING4 region required for p53 binding
    • Did not establish whether p53 enhancement occurs within a HAT complex
  2. 2004 High

    Identified NF-κB p65/RelA as a second direct target and linked ING4 to suppression of tumor angiogenesis, broadening its role beyond p53.

    Evidence Co-IP with p65, gene expression analysis, and brain tumor xenograft

    PMID:15029197

    Open questions at the time
    • Chromatin-level mechanism of repression not yet defined
    • Relationship to the p53 pathway unresolved
  3. 2005 Medium

    Defined the NLS region as the p53-binding determinant and showed ING4 represses HIF transcriptional activity via prolyl hydroxylase association, expanding its target repertoire to the hypoxic response.

    Evidence GST pulldown and NLS mutagenesis for p53; Co-IP with PHD/HPH and HIF reporter with stability controls

    PMID:15882981 PMID:15897452

    Open questions at the time
    • Single-lab NLS mapping
    • Did not resolve whether HIF repression is direct or chromatin-mediated
  4. 2006 High

    Provided the structural basis for chromatin reading by ING4, answering how it is targeted to active promoters and distinguishing it from the phosphoinositide-binding ING2.

    Evidence NMR structure of the PHD finger with methylated histone and phosphoinositide binding assays

    PMID:17157298

    Open questions at the time
    • Did not connect H3K4me3 reading to a specific enzymatic complex
    • Functional consequence of reading not yet shown
  5. 2008 High

    Resolved how ING4 represses NF-κB without blocking its activation: it remodels the chromatin environment at target promoters rather than preventing p65 DNA binding.

    Evidence ChIP, Co-IP, and siRNA showing reduced p300/acetyl-histone/H3K4me3 and increased HDAC-1 at promoters

    PMID:18779315

    Open questions at the time
    • Did not identify the acetyltransferase complex delivering ING4 to these promoters
    • Splice-variant and localization control addressed separately
  6. 2009 High

    Unified the chromatin-reading and acetylation activities by showing ING4 is a native HBO1 HAT subunit whose PHD-H3K4me3 engagement augments H3 acetylation and is required for genotoxic apoptosis.

    Evidence Co-IP, in vitro HAT reconstitution, ChIP, PHD mutagenesis, and anchorage-independent growth assay

    PMID:19187765

    Open questions at the time
    • Stoichiometry and architecture of ING4 within the complex not defined
    • Did not address dimerization
  7. 2012 High

    Defined the oligomeric architecture of ING4, showing an antiparallel coiled-coil homodimer that presents two PHD fingers for bivalent recognition and is functionally required for apoptosis.

    Evidence NMR of full-length protein, analytical ultracentrifugation, crystal structure of the dimerization domain, and dimerization mutant apoptosis assays

    PMID:20053357 PMID:22334692

    Open questions at the time
    • Did not show bivalent engagement on nucleosomal arrays
    • Link between dimerization and HBO1 targeting inferred, not directly measured
  8. 2013 Medium

    Extended ING4 mechanism to post-transcriptional and paracrine control, showing translational MYC repression via AUF1 and an H3K4me3/p53-dependent fibroblast secretory phenotype affecting tumor growth.

    Evidence Co-IP and mRNP-IP with AUF1 on MYC mRNA; PHD-mutant and p53-dependency assays with co-injection xenografts

    PMID:23603392 PMID:23604125

    Open questions at the time
    • AUF1-MYC mechanism not reconstituted
    • Paracrine secretory program direction (tumor-promoting vs suppressing) context-dependent
  9. 2015 High

    Identified the degradation machinery for ING4, showing SCF(JFK) ubiquitinates and destabilizes it and that this destabilization hyperactivates NF-κB to drive metastasis.

    Evidence Co-IP, in vitro ubiquitination, stability assays, and in vivo metastasis model

    PMID:25792601

    Open questions at the time
    • Upstream signal triggering JFK targeting not defined here
    • Degradation site not yet mapped
  10. 2019 Medium

    Connected ING4 chromatin function to ribosome biogenesis, showing PHD-dependent nucleolar localization at active rDNA promotes H3K9ac, UBF occupancy, and rRNA transcription.

    Evidence Immunofluorescence, CRISPR/RNAi deficiency, ChIP for H3K9ac/UBF, and rescue by re-expression

    PMID:31754246

    Open questions at the time
    • Whether HBO1/KAT complex mediates rDNA acetylation not shown
    • Single-lab finding
  11. 2024 High

    Established physiological developmental and stem-cell roles, showing ING4/ING5 are required for KAT6/KAT7-dependent H3K14/H3K23 acetylation in cardiac development and that ING4 regulates HSC quiescence and self-renewal.

    Evidence Mouse Ing4/Ing5 knockout genetics with histone modification ChIP/Western, cardiac phenotyping, HSC transcriptomics and competitive transplantation

    PMID:38446206 PMID:39175773

    Open questions at the time
    • Direct in vivo target promoters of ING4 in these tissues not catalogued
    • Mechanism linking ING4 loss to the HSC poised state undefined
  12. 2023 Medium

    Resolved the kinase signal upstream of ING4 degradation and a new functional consequence, showing CK2 phosphorylation at Ser-150 licenses JFK-mediated degradation and that stabilized ING4 promotes PD-L1 autophagic clearance to limit immune escape.

    Evidence CK2 knockout, phospho-site mapping, ubiquitination/stability assays, PD-L1 degradation and T-cell co-culture assays

    PMID:37870169

    Open questions at the time
    • Mechanism linking ING4 to PD-L1 autophagy not molecularly defined
    • Single-lab finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ING4's distinct activities — HBO1/KAT-complex acetylation, p53 cofactor function, NF-κB repression, and nucleolar rRNA control — are coordinated and prioritized in a given cell state remains unresolved.
  • No genome-wide map distinguishing direct ING4-HBO1 targets from p53/NF-κB-dependent ones
  • Quantitative partitioning of ING4 among its protein partners unknown
  • No human Mendelian disease link established in this corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0042393 histone binding 4 GO:0140110 transcription regulator activity 4 GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 2 GO:0003723 RNA binding 1
Localization
GO:0005634 nucleus 3 GO:0005730 nucleolus 2 GO:0005829 cytosol 1
Pathway
R-HSA-5357801 Programmed Cell Death 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-4839726 Chromatin organization 3
Partners
AUF1EGLN1EP300JFKKAT7RELASIRT1TP53
Complex memberships
HBO1/KAT7 histone acetyltransferase complexKAT6A/KAT6B/KAT7 HAT complexSCF(JFK) E3 ubiquitin ligase complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 ING4 (p29ING4) physically interacts with p300 (a histone acetyltransferase complex component) and p53 in vivo, enhances p53 acetylation at Lys-382, activates the p21/WAF1 promoter, and induces p53-dependent apoptosis and cell cycle arrest. Co-immunoprecipitation, p21/WAF1 promoter reporter assay, colony formation, flow cytometry Cancer research High 12750254
2004 ING4 physically interacts with the p65 (RelA) subunit of NF-κB and represses transcription of NF-κB-responsive genes, thereby regulating brain tumor angiogenesis. Co-immunoprecipitation, xenograft tumor model, gene expression analysis Nature High 15029197
2004 Overexpression of ING4 causes G2/M cell cycle arrest and upregulates p21 and Bax in a p53-dependent manner in HepG2 cells, and enhances chemosensitivity to etoposide and doxorubicin. Flow cytometry, Western blot, colony formation assay in p53-deficient (Saos-2) vs. p53-proficient (HepG2) cells FEBS letters Medium 15251430
2005 ING4 directly associates with the HIF prolyl hydroxylase (PHD/HPH) and represses HIF transcriptional activity without affecting HIF protein stability, providing a mechanism for ING4 regulation of the hypoxic response. Co-immunoprecipitation, HIF transcriptional reporter assay, protein stability analysis Proceedings of the National Academy of Sciences of the United States of America High 15897452
2005 The nuclear localization signal (NLS) region of ING4 is essential for its binding to p53; mutations or deletion of the NLS disrupt the ING4–p53 interaction in vitro and in vivo and abolish p21 upregulation. GST pulldown, co-immunoprecipitation, NLS mutagenesis, subcellular localization imaging Biochemical and biophysical research communications Medium 15882981
2006 The ING4 PHD finger structure was determined by NMR; ING4 PHD binds histone H3 trimethylated at K4 (H3K4me3) but, unlike ING2, does not bind phosphoinositides. NMR structure determination, binding assays with methylated histone peptides and phosphoinositides FEBS letters High 17157298
2006 ING4 splice variants lacking a full NLS show increased cytoplasmic localization, attenuated p21/WAF1 promoter activation, and altered cell spreading and migration suppression; ING4_v4 acts as a dominant-negative for p21 induction and cell motility suppression. ING4 variants also bind differentially to cytoplasmic proteins liprin-α1 and G3BP2a. Subcellular localization imaging, p21 promoter reporter assay, cell migration/spreading assay, co-immunoprecipitation The Journal of biological chemistry Medium 16973615
2007 ING4 directly interacts with HIF prolyl hydroxylase 2 (HPH-2/PHD2), suppresses HIF-1α activity and its target gene expression (NIP-3), and thereby reduces IL-8 and OPN proangiogenic molecule production in multiple myeloma cells. Co-immunoprecipitation, HIF reporter assay, siRNA knockdown, in vitro tube formation assay Blood Medium 17848618
2007 ING4 is expressed in ROMK-positive renal tubules; ING4 expression increases p38 and ERK MAPK phosphorylation, and ING4 reduces renal outer medullary K+ (ROMK) channel current in Xenopus oocytes through MAPK stimulation in response to low dietary K+ intake. siRNA knockdown, Western blot for phospho-MAPK, Xenopus oocyte electrophysiology, immunocytochemistry Proceedings of the National Academy of Sciences of the United States of America Medium 17517644
2008 ING4 and NF-κB bind simultaneously at NF-κB-regulated promoters; ING4 does not prevent NF-κB activation, nuclear translocation, or DNA binding but reduces p65 phosphorylation, p300, acetylated histones, and H3Me3K4 levels at target promoters while enhancing HDAC-1 recruitment. Chromatin immunoprecipitation (ChIP), Co-IP, siRNA knockdown, reporter assays Molecular and cellular biology High 18779315
2008 ING4 overexpression suppresses melanoma cell migration by ~63% and inhibits RhoA GTPase activity and ROCK-mediated stress fiber formation, and inhibits invasion by ~43% with reduced MMP-2 and MMP-9 activity. Cell migration/invasion assay, RhoA GTPase activity assay, zymography for MMP-2/9, overexpression Carcinogenesis Medium 18375955
2008 ING4 splice variant localization is modulated by two wobble-splicing events at the exon 4–5 boundary; ING4_v1 localizes to the nucleolus (containing an intrinsic nucleolar localization signal), and nucleolar accumulation prolongs ING4 half-life. ING4 is degraded via the ubiquitin-proteasome pathway and subjected to N-terminal ubiquitination. Subcellular localization imaging, protein half-life assay, proteasome inhibitor treatment, ubiquitination assay Experimental cell research Medium 18775696
2009 ING4 is a native subunit of the HBO1 histone acetyltransferase (HAT) complex. The ING4 PHD finger specifically recognizes H3K4me3, and this interaction augments HBO1 acetyltransferase activity on H3 tails and drives H3 acetylation at ING4 target promoters. ING4–H3K4me3 interaction is required for ING4-dependent apoptosis after genotoxic stress and inhibition of anchorage-independent growth. Co-immunoprecipitation, in vitro HAT assay, ChIP, PHD finger mutagenesis, anchorage-independent growth assay Molecular cell High 19187765
2010 ING4 forms homodimers through its N-terminal coiled-coil domain; the dimer has two independent H3K4me3-binding PHD fingers, suggesting bivalent chromatin recognition to enhance HBO1 complex targeting. Monomeric ING4 mutants lose the ability to induce apoptosis after genotoxic stress. NMR of full-length protein, analytical ultracentrifugation, H3K4me3 binding assay, dimerization mutagenesis, apoptosis assay Journal of molecular biology High 20053357
2010 ING4 expression is induced by the metastasis suppressor BRMS1; ING4 knockdown abrogates BRMS1-mediated suppression of HUVEC growth and IL-6 expression, placing ING4 downstream of BRMS1 in the suppression of melanoma angiogenesis via NF-κB/IL-6 axis. siRNA knockdown, epistasis by rescue experiments, HUVEC tube formation assay, in vivo matrigel plug assay Cancer research Medium 21056991
2011 PAD4 citrullinates ING4 preferentially within its NLS region, disrupting the ING4–p53 interaction. A citrulline-mimicking Arg→Gln NLS mutant of ING4 loses p53 binding, fails to promote p53 acetylation, represses p21 expression, and is more susceptible to proteasomal degradation. In vitro citrullination assay, Co-IP, site-directed mutagenesis, Western blot for p21/acetylated p53, protein stability assay The Journal of biological chemistry High 21454715
2012 Crystal structure of the ING4 N-terminal dimerization domain reveals an antiparallel coiled-coil homodimer with helix-loop-helix protomers. Monomeric mutants lose the ability to induce apoptosis after genotoxic stress, demonstrating that dimerization is functionally required for tumor suppressor activity. X-ray crystallography (2.3 Å resolution), dimerization mutagenesis, apoptosis assay The Journal of biological chemistry High 22334692
2012 ING4 negatively regulates NF-κB in breast cancer by inhibiting p65/RelA phosphorylation; ectopic ING4 expression suppresses PMA-induced invasion and NF-κB target gene expression in T47D and MCF7 breast cancer cells. Ectopic overexpression, Western blot for phospho-p65, invasion assay, gene expression analysis PloS one Medium 23056468
2013 ING4 binds directly to AUF1; the ING4–AUF1 complex associates with MYC mRNA (shown by mRNP immunoprecipitation), and ING4 suppresses MYC protein expression without altering MYC mRNA levels, indicating translational repression. Co-immunoprecipitation, mRNP immunoprecipitation, Western blot, qRT-PCR FEBS letters Medium 23603392
2013 ING4 regulates a chemokine secretory phenotype in primary fibroblasts in a p53-dependent and H3K4me3-recognition-dependent manner; this phenotype selectively promotes tumor cell proliferation in a paracrine fashion in vitro and promotes tumor growth in co-injection in vivo assays. Gene expression analysis, PHD finger mutant, p53 dependency, in vitro co-culture proliferation, in vivo co-injection xenograft Oncogene Medium 23604125
2013 HPV16 E6 oncoprotein binds ING4 in vivo and in vitro, attenuating ING4-induced p53 acetylation and the ING4–p53 interaction independently of p53 degradation, thereby diminishing ING4-enhanced p53-mediated apoptosis. Co-immunoprecipitation (in vivo and in vitro), p53 acetylation Western blot, apoptosis assay PloS one Medium 23967213
2014 ING4 expression is transiently induced by Myc during prostate epithelial differentiation from basal to luminal cells; Pten loss blocks ING4 expression, and re-expression of ING4 rescues Pten-loss-induced differentiation defects. Loss of ING4 (directly or via Pten loss) prevents luminal differentiation and promotes tumorigenesis downstream of Myc. Genetic epistasis (Pten KO rescue by ING4 re-expression), 3D organoid differentiation assay, tumor xenograft, IHC of human tumors Cancer research Medium 24762396
2015 JFK is an F-box protein that targets ING4 for ubiquitination and proteasomal degradation by assembling an SCF(JFK) E3 ubiquitin ligase complex. JFK-mediated ING4 destabilization leads to hyperactivation of canonical NF-κB signaling and promotes breast cancer angiogenesis and metastasis. Co-immunoprecipitation, ubiquitination assay, protein stability assay, siRNA knockdown, in vivo metastasis model Genes & development High 25792601
2015 ING4 inhibits estrogen-independent ER activity in breast cancer cells; ING4 overexpression represses selective ER-target gene transcription without affecting nuclear ERα protein levels, and increases sensitivity of ER+ cells to hormone deprivation. ER-target gene expression analysis, hormone deprivation assay, overexpression in T47D and MCF7 cells, fulvestrant vs. tamoxifen comparison Breast cancer (Dove Medical Press) Low 27895513
2019 ING4 suppresses HCC growth and metastasis via a NF-κB/miR-155/FOXO3a pathway: ING4 represses NF-κB transcriptional activity, thereby reducing miR-155 expression, which relieves miR-155-mediated suppression of FOXO3a, increasing FOXO3a nuclear level and transcriptional activity. Lentiviral overexpression and knockdown, luciferase reporter for NF-κB, miR-155 overexpression/inhibition rescue experiments, in vivo xenograft International journal of biological sciences Medium 30745827
2019 ING4 localizes strongly to the nucleolus via its PHD domain (which binds H3K4me3 at active rDNA promoters); ING4-deficient cells show reduced H3K9 acetylation and UBF occupancy at rDNA promoters, reduced rRNA transcription, and altered nucleolar structure, all rescued by GFP-ING4 re-expression. Immunofluorescence/nucleolar localization, CRISPR/RNAi-mediated ING4 deficiency, ChIP for H3K9ac and UBF, rRNA transcription assay, rescue by re-expression Scientific reports Medium 31754246
2020 ING4 directly interacts with SIRT1 (shown by immunoprecipitation) and blocks NF-κB p65 nuclear translocation and p65 acetylation at K310 in LPS-stimulated macrophages, providing an anti-inflammatory mechanism via an ING4/SIRT1/NF-κB axis. Co-immunoprecipitation, Western blot for nuclear p65 and acetyl-p65 K310, LPS macrophage model in vitro and in vivo Immunology and cell biology Medium 31811786
2021 Cxcl10-induced migration of ING4-deleted breast cancer cells requires a physical or proximal association between Cxcr3 and Egfr receptors (shown by immunofluorescent colocalization) and downstream Gβγ signaling; ING4-intact cells do not sustain the Cxcr3/Egfr colocalization or migration response. Immunofluorescent receptor colocalization, pharmacological inhibitors of Cxcr3/Egfr/Gβγ, ING4-deletion cell line, cell migration assay Molecular and cellular biology Medium 34871062
2023 CK2 (casein kinase 2) phosphorylates ING4 at Ser-150, triggering ING4 ubiquitination and degradation by the JFK E3 ubiquitin ligase. CK2 knockout increases ING4 protein stability and enhances T cell anti-tumor activity by allowing ING4-dependent PD-L1 autophagic degradation, thereby suppressing NSCLC immune escape. CK2 knockout, phospho-site mapping (ING4-S150), ubiquitination assay, protein stability assay, PD-L1 expression/autophagic degradation assay, T cell co-culture assay Advanced science Medium 37870169
2024 ING4 and ING5 are essential components of the KAT6A/KAT6B/KAT7 HAT complexes required for histone H3K14 acetylation and H3K23 acetylation; Ing4/Ing5 double-knockout embryos show loss of H3K14ac and reduced H3K23ac. ING4/ING5 are required for epicardial cell lineage development and proepicardium outgrowth, with Ing4+/−Ing5−/− hearts showing epicardial and coronary vasculature defects. Mouse knockout genetics, histone modification Western blot/ChIP, cardiac phenotype analysis, cell adhesion gene expression Development High 38446206
2024 Ing4 deficiency in hematopoietic stem cells (HSCs) promotes a transcriptionally poised state with gene expression signatures of activation yet G0 arrest; Ing4-deficient HSCs show enhanced regenerative capacity after transplantation, indicating ING4 regulates HSC quiescence and self-renewal balance. Mouse Ing4 knockout, transcriptome analysis, cell cycle analysis (G0 markers), competitive transplantation assay iScience Medium 39175773
2010 A cancer-associated ING4 mutant (N214D) found in human tumors shows dramatically reduced ability to inhibit proliferation, anchorage-independent growth, and cell migration, and sensitize to cell death; the functional impairment correlates with reduced protein stability due to increased proteasome-mediated degradation, not with altered H3K4me3 binding or folding. Mutagenesis, protein stability assay, proteasome inhibitor rescue, proliferation/migration/soft agar assays, histone binding assay Carcinogenesis Medium 20705953

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis. Nature 291 15029197
2003 p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity. Cancer research 240 12750254
2009 ING4 mediates crosstalk between histone H3 K4 trimethylation and H3 acetylation to attenuate cellular transformation. Molecular cell 172 19187765
2005 The candidate tumor suppressor ING4 represses activation of the hypoxia inducible factor (HIF). Proceedings of the National Academy of Sciences of the United States of America 147 15897452
2007 Curcumin induces G2/M cell cycle arrest in a p53-dependent manner and upregulates ING4 expression in human glioma. Journal of neuro-oncology 126 17594054
2004 A screen for genes that suppress loss of contact inhibition: identification of ING4 as a candidate tumor suppressor gene in human cancer. Proceedings of the National Academy of Sciences of the United States of America 119 15528276
2007 The new tumor-suppressor gene inhibitor of growth family member 4 (ING4) regulates the production of proangiogenic molecules by myeloma cells and suppresses hypoxia-inducible factor-1 alpha (HIF-1alpha) activity: involvement in myeloma-induced angiogenesis. Blood 114 17848618
2005 Frequent deletion and down-regulation of ING4, a candidate tumor suppressor gene at 12p13, in head and neck squamous cell carcinomas. Gene 105 15935570
2011 Citrullination of inhibitor of growth 4 (ING4) by peptidylarginine deminase 4 (PAD4) disrupts the interaction between ING4 and p53. The Journal of biological chemistry 100 21454715
2008 Role of ING4 in human melanoma cell migration, invasion and patient survival. Carcinogenesis 99 18375955
2008 The ING4 tumor suppressor attenuates NF-kappaB activity at the promoters of target genes. Molecular and cellular biology 93 18779315
2010 MicroRNA-650 targets ING4 to promote gastric cancer tumorigenicity. Biochemical and biophysical research communications 92 20381459
2004 ING4 induces G2/M cell cycle arrest and enhances the chemosensitivity to DNA-damage agents in HepG2 cells. FEBS letters 91 15251430
2006 Novel splice variants of ING4 and their possible roles in the regulation of cell growth and motility. The Journal of biological chemistry 85 16973615
2005 Nuclear localization signal of ING4 plays a key role in its binding to p53. Biochemical and biophysical research communications 69 15882981
2008 Adenovirus-mediated ING4 expression suppresses lung carcinoma cell growth via induction of cell cycle alteration and apoptosis and inhibition of tumor invasion and angiogenesis. Cancer letters 57 18789575
2015 MiR-761 Promotes Progression and Metastasis of Non-Small Cell Lung Cancer by Targeting ING4 and TIMP2. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 53 26278569
2006 Solution structure and NMR characterization of the binding to methylated histone tails of the plant homeodomain finger of the tumour suppressor ING4. FEBS letters 49 17157298
2012 Upregulation of miR-650 is correlated with down-regulation of ING4 and progression of hepatocellular carcinoma. Journal of surgical oncology 46 22767438
2010 Cell cycle regulator ING4 is a suppressor of melanoma angiogenesis that is regulated by the metastasis suppressor BRMS1. Cancer research 46 21056991
2009 Reduced expression and novel splice variants of ING4 in human gastric adenocarcinoma. The Journal of pathology 43 19479822
2010 Down-regulation of ING4 is associated with initiation and progression of lung cancer. Histopathology 42 20716169
2019 ING4 suppresses hepatocellular carcinoma via a NF-κB/miR-155/FOXO3a signaling axis. International journal of biological sciences 39 30745827
2012 Negative regulation of NF-κB by the ING4 tumor suppressor in breast cancer. PloS one 39 23056468
2005 Regulation of HIF by prolyl hydroxylases: recruitment of the candidate tumor suppressor protein ING4. Cell cycle (Georgetown, Tex.) 38 16096374
2010 The dimeric structure and the bivalent recognition of H3K4me3 by the tumor suppressor ING4 suggests a mechanism for enhanced targeting of the HBO1 complex to chromatin. Journal of molecular biology 36 20053357
2015 SCF(JFK) is a bona fide E3 ligase for ING4 and a potent promoter of the angiogenesis and metastasis of breast cancer. Genes & development 34 25792601
2010 Enhanced antitumor activity by combining an adenovirus harboring ING4 with cisplatin for hepatocarcinoma cells. Cancer gene therapy 34 21052098
2007 Detection of novel mRNA splice variants of human ING4 tumor suppressor gene. Oncogene 33 17325660
2009 Adenovirus-mediated ING4 expression suppresses pancreatic carcinoma cell growth via induction of cell-cycle alteration, apoptosis, and inhibition of tumor angiogenesis. Cancer biotherapy & radiopharmaceuticals 32 19409049
2012 Identification of ING4 (inhibitor of growth 4) as a modulator of docetaxel sensitivity in human lung adenocarcinoma. Molecular medicine (Cambridge, Mass.) 31 22460125
2019 Long non-coding RNA FENDRR restrains the aggressiveness of CRC via regulating miR-18a-5p/ING4 axis. Journal of cellular biochemistry 30 31724220
2014 Transient induction of ING4 by Myc drives prostate epithelial cell differentiation and its disruption drives prostate tumorigenesis. Cancer research 30 24762396
2012 Enhanced radiosensitivity of non-small-cell lung cancer (NSCLC) by adenovirus-mediated ING4 gene therapy. Cancer gene therapy 30 22863759
2008 Two wobble-splicing events affect ING4 protein subnuclear localization and degradation. Experimental cell research 30 18775696
2011 Enhanced tumor suppression by an ING4/IL-24 bicistronic adenovirus-mediated gene cotransfer in human non-small cell lung cancer cells. Cancer gene therapy 29 21660060
2014 Delivery of inhibitor of growth 4 (ING4) gene significantly inhibits proliferation and invasion and promotes apoptosis of human osteosarcoma cells. Scientific reports 28 25490312
2019 miR-650 promotes non-small cell lung cancer cell proliferation and invasion by targeting ING4 through Wnt-1/β-catenin pathway. Oncology letters 27 31611970
2011 Deletion of the inhibitor of growth 4 (ING4) tumor suppressor gene is prevalent in human epidermal growth factor 2 (HER2)-positive breast cancer. Human pathology 27 21315418
2010 A dominant mutant allele of the ING4 tumor suppressor found in human cancer cells exacerbates MYC-initiated mouse mammary tumorigenesis. Cancer research 27 20501848
2008 ING4 induces cell growth inhibition in human lung adenocarcinoma A549 cells by means of Wnt-1/beta-catenin signaling pathway. Anatomical record (Hoboken, N.J. : 2007) 27 18399550
2012 Expression of hypoxia-inducible factor (HIF)-1a-vascular endothelial growth factor (VEGF)-inhibitory growth factor (ING)-4- axis in sarcoidosis patients. BMC research notes 25 23181555
2012 Expression of tumor suppressor gene ING4 in ovarian carcinoma is correlated with microvessel density. Journal of cancer research and clinical oncology 24 22228137
2011 Downregulation and translocation of nuclear ING4 is correlated with tumorigenesis and progression of head and neck squamous cell carcinoma. Oral oncology 23 21310648
2013 Tumor suppressor ING4 overexpression contributes to proliferation and invasion inhibition in gastric carcinoma by suppressing the NF-κB signaling pathway. Molecular biology reports 22 24057236
2012 Crystal structure of inhibitor of growth 4 (ING4) dimerization domain reveals functional organization of ING family of chromatin-binding proteins. The Journal of biological chemistry 22 22334692
2012 ING4 is negatively correlated with microvessel density in colon cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 22 23055189
2023 Inhibition of CK2/ING4 Pathway Facilitates Non-Small Cell Lung Cancer Immunotherapy. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 21 37870169
2009 Loss of inhibitor of growth (ING-4) is implicated in the pathogenesis and progression of human astrocytomas. Brain pathology (Zurich, Switzerland) 21 19775294
2019 MicroRNA‑214 upregulates HIF‑1α and VEGF by targeting ING4 in lung cancer cells. Molecular medicine reports 19 31059086
2013 Autophagy contributes to ING4-induced glioma cell death. Experimental cell research 19 23684856
2010 Functional impact of cancer-associated mutations in the tumor suppressor protein ING4. Carcinogenesis 19 20705953
2019 The essential role of tumor suppressor gene ING4 in various human cancers and non-neoplastic disorders. Bioscience reports 17 30643005
2012 Effect of the tumor suppressor gene ING4 on the proliferation of MCF-7 human breast cancer cells. Oncology letters 17 22970041
2012 Radiosensitivity by ING4-IL-24 bicistronic adenovirus-mediated gene cotransfer on human breast cancer cells. Cancer gene therapy 17 23175244
2011 Downregulated expression of inhibitor of growth 4 (ING4) in advanced colorectal cancers: a non-randomized experimental study. Pathology oncology research : POR 17 21626442
2017 Roles of microRNA-330 and Its Target Gene ING4 in the Development of Aggressive Phenotype in Hepatocellular Carcinoma Cells. Digestive diseases and sciences 16 28050784
2014 Adenovirus-mediated ING4 Gene Transfer in Osteosarcoma Suppresses Tumor Growth via Induction of Apoptosis and Inhibition of Tumor Angiogenesis. Technology in cancer research & treatment 16 25326586
2013 ING4 inhibits the translation of proto-oncogene MYC by interacting with AUF1. FEBS letters 16 23603392
2013 The ING4 Binding with p53 and Induced p53 Acetylation were Attenuated by Human Papillomavirus 16 E6. PloS one 16 23967213
2021 Polyethylenimine-Modified Bombyx mori Silk Fibroin as a Delivery Carrier of the ING4-IL-24 Coexpression Plasmid. Polymers 15 34685354
2021 Cxcl10 Chemokine Induces Migration of ING4-Deficient Breast Cancer Cells via a Novel Cross Talk Mechanism between the Cxcr3 and Egfr Receptors. Molecular and cellular biology 14 34871062
2017 Efficacy of combining ING4 and TRAIL genes in cancer-targeting gene virotherapy strategy: first evidence in preclinical hepatocellular carcinoma. Gene therapy 14 28925992
2017 ING4 expressing oncolytic vaccinia virus promotes anti-tumor efficiency and synergizes with gemcitabine in pancreatic cancer. Oncotarget 14 29137298
2013 ING4 regulates a secretory phenotype in primary fibroblasts with dual effects on cell proliferation and tumor growth. Oncogene 14 23604125
2015 Adenovirus-mediated ING4/PTEN double tumor suppressor gene co-transfer modified by RGD enhances antitumor activity in human nasopharyngeal carcinoma cells. International journal of oncology 13 25571952
2015 Adenovirus-mediated p53 and ING4 gene co-transfer elicits synergistic antitumor effects through enhancement of p53 acetylation in breast cancer. Oncology reports 13 26530780
2020 ING4 alleviated lipopolysaccharide-induced inflammation by regulating the NF-κB pathway via a direct interaction with SIRT1. Immunology and cell biology 12 31811786
2019 Inhibitor of Growth 4 (ING4) is a positive regulator of rRNA synthesis. Scientific reports 12 31754246
2016 Combinatorial strategies based on CRAd-IL24 and CRAd-ING4 virotherapy with anti-angiogenesis treatment for ovarian cancer. Journal of ovarian research 12 27349517
2015 Synergistic tumor suppression by adenovirus-mediated ING4/PTEN double gene therapy for gastric cancer. Cancer gene therapy 12 26564429
2020 ING4 Expression Landscape and Association With Clinicopathologic Characteristics in Breast Cancer. Clinical breast cancer 11 33334698
2019 Inhibitor of growth 4 (ING4) inhibits hypoxia-induced EMT by decreasing HIF-1α and snail in HK2 cells. Acta histochemica 11 31239073
2019 Oncogenic microRNA-765 promotes the growth and metastasis of breast carcinoma by directly targeting ING4. Journal of cellular biochemistry 11 31724215
2019 Cationic Antheraea pernyi Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells. International journal of nanomedicine 11 31849466
2018 Differential cellular localization of CELSR2 and ING4 and correlations with hormone receptor status in breast cancer. Histology and histopathology 11 29489009
2018 N-methyl-N-nitro-N-nitrosoguanidine-mediated ING4 downregulation contributed to the angiogenesis of transformed human gastric epithelial cells. Life sciences 11 29496496
2012 Adenovirus-mediated ING4/IL-24 double tumor suppressor gene co-transfer enhances antitumor activity in human breast cancer cells. Oncology reports 11 22842937
2009 Down-regulation of the inhibitor of growth family member 4 (ING4) in different forms of pulmonary fibrosis. Respiratory research 11 19250543
2016 ING4 Inhibits Proliferation and Induces Apoptosis in Human Melanoma A375 Cells via the Fas/Caspase-8 Apoptosis Pathway. Dermatology (Basel, Switzerland) 10 27070489
2016 Co-expression of ING4 and P53 enhances hypopharyngeal cancer chemosensitivity to cisplatin in vivo. Molecular medicine reports 10 27484725
2015 Recombinant ING4 suppresses the migration of SW579 thyroid cancer cells via epithelial to mesenchymal transition. Experimental and therapeutic medicine 10 26622361
2015 ING4 enhances paclitaxel's effect on colorectal cancer growth in vitro and in vivo. International journal of clinical and experimental pathology 9 26045800
2007 Inhibitor of growth 4 (ING4) is up-regulated by a low K intake and suppresses renal outer medullary K channels (ROMK) by MAPK stimulation. Proceedings of the National Academy of Sciences of the United States of America 9 17517644
2016 Tumor suppressor ING4 inhibits estrogen receptor activity in breast cancer cells. Breast cancer (Dove Medical Press) 8 27895513
2014 Adenovirus-mediated ING4 Gene Transfer in Osteosarcoma Suppresses Tumor Growth via Induction of Apoptosis and Inhibition of Tumor Angiogenesis. Technology in cancer research & treatment 8 24750000
2013 Adenovirus-mediated ING4 expression reduces multidrug resistance of human gastric carcinoma cells in vitro and in vivo. Oncology reports 8 23969950
2024 ING4 and ING5 are essential for histone H3 lysine 14 acetylation and epicardial cell lineage development. Development (Cambridge, England) 7 38446206
2017 Expression of ING4 is negatively correlated with cellular proliferation and microvessel density in human glioma. Oncology letters 7 28927128
2021 Correlation analysis of survivin, ING4, CXCL8 and VEGF expression in prostate cancer tissue. American journal of translational research 6 35035717
2016 Adenovirus-mediated co-expression of ING4 and PTEN cooperatively enhances their antitumor activity in human hepatocellular carcinoma cells. Acta biochimica et biophysica Sinica 6 27421660
2015 Reduced ING4 Expression Is Associated with the Malignancy of Human Bladder. Urologia internationalis 6 25790869
2015 Oncogenic Ras suppresses ING4-TDG-Fas axis to promote apoptosis resistance. Oncotarget 6 26544625
2014 Experimental studies on the inhibition of adenovirus-ING4-OSM therapy on nasopharyngeal carcinoma proliferation in vitro and in vivo. Cell biochemistry and biophysics 6 25005773
2024 Ing4-deficiency promotes a quiescent yet transcriptionally poised state in hematopoietic stem cells. iScience 5 39175773
2022 Enhanced effect of recombinant adenoviruses co-expression of ING4 and OSM on anti-tumour activity of laryngeal cancer. Journal of cellular and molecular medicine 5 35075768
2022 Inhibitor of Growth 4 (ING4) Plays a Tumor-repressing Role in Oral Squamous Cell Carcinoma via Nuclear Factor Kappa-B (NF-kB)/DNA Methyltransferase 1 (DNMT1) Axis-mediated Regulation of Aldehyde Dehydrogenase 1A2 (ALDH1A2). Current cancer drug targets 5 35388759
2019 Autoantibodies against P29ING4 are associated with complex regional pain syndrome. Immunologic research 5 32008173
2010 Crystallization and preliminary X-ray diffraction analysis of the dimerization domain of the tumour suppressor ING4. Acta crystallographica. Section F, Structural biology and crystallization communications 5 20445261
2009 [In vitro and in vivo inhibitory effect of Ad-ING4 gene on proliferation of human prostate cancer PC-3 cells]. Ai zheng = Aizheng = Chinese journal of cancer 5 19895734

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