Affinage

ING1

Inhibitor of growth protein 1 · UniProt Q9UK53

Length
422 aa
Mass
46.7 kDa
Annotated
2026-06-10
100 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ING1 is a nuclear tumor suppressor that couples epigenetic chromatin reading to the control of proliferation, senescence, DNA repair, and apoptosis (PMID:8944021, PMID:9121449, PMID:18533182). Its PHD finger is a sequence-specific reader of histone H3 trimethylated at Lys4 (H3K4me3): a 2.1 Å structure shows Y212 and W235 forming a hydrophobic pocket that engages the trimethylammonium group through cation-π contacts, and cancer-associated PHD mutations abolish H3K4me3 binding and disable ING1's ability to stimulate DNA repair and promote apoptosis (PMID:18533182). Through this reader function ING1 docks chromatin-modifying machinery, partitioning between activating histone acetyltransferase complexes (NuA4/Tra1, TRRAP/PCAF/CBP/p300), which it uses to drive H3/H4 hyperacetylation in an isoform-specific manner, and repressive Sin3-HDAC1 complexes, which the p33ING1b N-terminus engages directly via SAP30 to silence transcription (PMID:10805724, PMID:11604499, PMID:12015309, PMID:11784859). ING1 acts largely in concert with p53: it physically associates with p53, cooperates to transactivate p21WAF1 and drive growth arrest, stabilizes wild-type p53 by binding ubiquitin through a UBD and recruiting the deubiquitinase HAUSP to block polyubiquitination, and is required for oncogene-induced senescence and p53-dependent heterochromatin formation (PMID:9440695, PMID:17693408, PMID:21078114, PMID:21731648). The shorter and longer ING1 isoforms have opposing effects on p53, so a single locus encodes both p53-activating and p53-suppressing proteins (PMID:10542254). ING1 also operates p53-independently, suppressing proliferation, inducing Bax, and translocating to mitochondria where, via a BH3-like domain, it interacts with BAX to promote apoptosis (PMID:17332334, PMID:24008732). ING1 activity is gated by localization and stability: it requires a lamin-A interaction domain and karyopherin-dependent nuclear import, undergoes UV-induced nucleolar translocation to bind PCNA (via a PIP domain) and CSIG to commit cells to apoptosis, and is regulated by phosphorylation at Ser-126 (by Chk1 and Cdk1) that stabilizes it through NQO1, while 14-3-3 binding and Src-mediated phosphorylation drive cytoplasmic sequestration that blocks its function (PMID:11682605, PMID:11353074, PMID:16581770, PMID:17585055, PMID:18836436, PMID:18655775, PMID:18388957, PMID:22419112, PMID:23585863). At the nucleolus ING1b recruits HDAC1 and the NoRC complex to rDNA to deacetylate active marks and repress rRNA transcription (PMID:27903908).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1996 Medium

    Established ING1 as a candidate tumor suppressor by showing its expression bidirectionally controls cell growth, addressing whether the gene actively restrains proliferation.

    Evidence Subtractive/GSE cloning with overexpression and chronic antisense in cell lines

    PMID:8944021

    Open questions at the time
    • No molecular mechanism for growth inhibition
    • Single lab functional readouts
    • No in vivo tumor data
  2. 1997 Medium

    Linked ING1 to senescence and apoptosis, defining the cellular programs it engages beyond simple growth inhibition.

    Evidence Immunofluorescence localization, expression quantification in senescent fibroblasts, and antisense/overexpression apoptosis assays

    PMID:9102209 PMID:9121449 PMID:9186514

    Open questions at the time
    • No molecular effectors identified
    • Mechanism of senescence/apoptosis induction unknown
  3. 1998 High

    Showed ING1 physically and functionally cooperates with p53 to activate p21WAF1, placing it within the p53 growth-arrest pathway.

    Evidence Co-IP, p21/WAF1 promoter-reporter assays, and antisense/dominant-negative epistasis

    PMID:9440695

    Open questions at the time
    • Direct vs indirect p53 binding not resolved
    • Did not address p53-independent functions
  4. 1999 Medium

    Revealed that the ING1 locus encodes isoforms with opposing effects on p53, explaining functional heterogeneity within the gene.

    Evidence Co-IP and p53-responsive reporter assays after DNA damage with mouse isoforms

    PMID:10542254

    Open questions at the time
    • Mechanistic basis of opposing isoform activity unclear
    • Mouse ortholog only
  5. 2000 High

    Connected ING1-family proteins to histone acetyltransferase and Sin3-HDAC corepressor complexes, defining ING1 as a chromatin-modifying complex component.

    Evidence Yeast two-hybrid, Co-IP, HAT activity assays, genetic rescue, in vitro HDAC assays, and reporter assays

    PMID:10805724 PMID:11118440

    Open questions at the time
    • How ING1 selects HAT vs HDAC complexes not defined
    • Chromatin targeting determinant unknown
  6. 2001 High

    Established the DNA-damage response axis of ING1, linking UV-induced PCNA binding and nucleolar targeting to commitment to apoptosis and DNA repair.

    Evidence PIP and NTS domain mutagenesis with apoptosis assays, host-cell reactivation repair assays, GADD45 Co-IP, and NuA4 reconstitution by MS in yeast

    PMID:11353074 PMID:11431327 PMID:11604499 PMID:11682605

    Open questions at the time
    • How PCNA binding switches repair to apoptosis unresolved
    • Nucleolar effectors not yet identified
  7. 2002 High

    Mapped isoform-specific partitioning between acetylation-promoting and deacetylation-promoting complexes via direct SAP30 binding, defining how ING1 imposes activating or repressive chromatin states.

    Evidence Co-IP, in vitro HAT assays, in vivo acetylation imaging, complex purification, and domain-mapping growth suppression assays

    PMID:11784859 PMID:12015309

    Open questions at the time
    • Structural basis of complex selection not defined
    • Determinants directing isoform-specific partner choice unclear
  8. 2003 Medium

    Extended ING1's reach to SIRT1 inhibition and promoter-specific DNA binding, showing it tunes p53 acetylation and represses target promoters.

    Evidence EMSA, promoter-reporter assays, Co-IP, and p53 acetylation Western blots

    PMID:14522900

    Open questions at the time
    • Direct SIRT1 inhibition mechanism not structurally defined
    • Single lab
  9. 2005 Medium

    Defined two autonomous silencing domains with distinct HDAC dependence and showed oncogenic Ras enhances ING1 silencing, integrating signaling input into its repressive function.

    Evidence Deletion-mutant reporter assays with TSA and MAPK inhibitor treatment plus colony formation

    PMID:15601862

    Open questions at the time
    • Mechanism of HDAC-independent C-terminal silencing unknown
    • Direct Ras/MAPK target on ING1 not identified
  10. 2006 Medium

    Showed ING1 is subject to spatial and signaling regulation through ARF-driven nucleolar redistribution and phospho-dependent 14-3-3 cytoplasmic tethering that blocks its activity.

    Evidence Co-IP, phosphatase treatment, subcellular fractionation, ARF-knockout MEFs, and p21WAF1 readouts

    PMID:16581770 PMID:16607280

    Open questions at the time
    • Kinase generating the 14-3-3 site not defined here
    • Functional relationship of ARF and 14-3-3 control unresolved
  11. 2007 Medium

    Established phosphorylation- and genotype-dependent control of ING1, defining Ser-126 phosphorylation as a stability switch and demonstrating both p53-dependent senescence and p53-independent tumor suppression in vivo.

    Evidence In vitro kinase assays (Chk1/Cdk1), Ser126Ala mutagenesis with half-life measurement, and Ing1-knockout mice and MEFs

    PMID:17332334 PMID:17585055 PMID:17693408

    Open questions at the time
    • Effector pathway for p53-independent suppression incompletely defined
    • Mechanism connecting Ser-126 to stability not molecularly resolved at this stage
  12. 2008 High

    Provided the structural and trafficking framework for ING1 function, defining the PHD finger as an H3K4me3 reader and establishing lamin-A-, karyopherin-, and NQO1-dependent localization and stability control.

    Evidence X-ray crystallography with mutagenesis, peptide microarray, LMNA-knockout cells, NLS mutagenesis, and in vitro proteasomal degradation assays

    PMID:18388957 PMID:18533182 PMID:18655775 PMID:18836436

    Open questions at the time
    • How H3K4me3 reading is coupled to complex recruitment in vivo not fully defined
    • Hierarchy among localization controls unresolved
  13. 2010 Medium

    Identified chromatin-level transcriptional targets of ING1 (DGCR8) genome-wide, connecting its chromatin function to proliferation control.

    Evidence Expression microarray in Ing1-null MEFs, ChIP at the DGCR8 promoter, and proliferation assays

    PMID:20179197

    Open questions at the time
    • Direct vs indirect regulation of broader target set unclear
    • Chromatin complex used at DGCR8 not specified
  14. 2011 Medium

    Defined the molecular basis of ING1-mediated p53 stabilization and its role in p16INK4a-driven senescence, linking ubiquitin binding and HAUSP recruitment to tumor-suppressor output.

    Evidence Ubiquitin-binding/Kd measurements, ING1-HAUSP Co-IP, p53 ubiquitination assays, and p16 ChIP with curcumin inhibition

    PMID:21731648 PMID:21896275

    Open questions at the time
    • Whether HAUSP recruitment is constitutive or signal-induced not defined
    • Single lab for both findings
  15. 2013 Medium

    Broadened ING1 mechanism to DNA demethylation targeting, p53-independent mitochondrial apoptosis via BAX, and Src-driven cytoplasmic relocalization, defining cytoplasmic and chromatin axes beyond p53.

    Evidence Xenopus Ing1 knockdown with methylation/ChIP analysis, ING1-BAX Co-IP with mitochondria-targeted constructs, and Src in vitro kinase plus Co-IP and apoptosis assays

    PMID:23388825 PMID:23585863 PMID:24008732

    Open questions at the time
    • BH3-like domain function not structurally validated
    • Relationship between nuclear and mitochondrial pools unresolved
  16. 2017 Medium

    Established ING1 as a direct repressor of rRNA transcription, linking it to ribosome biogenesis control via HDAC1/NoRC recruitment and mTOR antagonism at the nucleolus.

    Evidence ChIP of ING1/HDAC1/NoRC at rDNA, Co-IP, rRNA quantification, and mTOR localization imaging with knockdown

    PMID:27903908

    Open questions at the time
    • Mechanism of ING1-mTOR/UBF antagonism not biochemically defined
    • Single lab
  17. 2021 Medium

    Showed ING1 mediates androgen-receptor-dependent repression of hTERT, extending its repressive chromatin role to hormone-regulated transcription.

    Evidence ChIP at the hTERT nARE, reporter assays, siRNA knockdown, and ex vivo patient samples

    PMID:34439179

    Open questions at the time
    • Whether ING1 reads a specific chromatin mark at the nARE not defined
    • Functional redundancy with ING2 unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the single H3K4me3-reading PHD finger is dynamically switched between activating HAT and repressive HDAC complexes, and how nuclear, nucleolar, and mitochondrial pools are coordinated during the damage response, remains unresolved.
  • No structural model of ING1 within an intact HAT or HDAC complex
  • Determinants of complex selection in vivo unknown
  • Quantitative coordination of subcellular pools during apoptosis not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0042393 histone binding 3 GO:0060090 molecular adaptor activity 3 GO:0003677 DNA binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005730 nucleolus 4 GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2 GO:0005829 cytosol 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-4839726 Chromatin organization 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-73894 DNA Repair 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
BAXGADD45AHDAC1LMNAPCNASAP30TP53USP7/HAUSP
Complex memberships
NoRCNuA4 HAT complexSin3-HDAC1 (mSin3A/SAP30/RbAp48)

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 ING1 (p33ING1) was identified as a nuclear growth inhibitor whose acute overexpression inhibits cell growth and whose chronic antisense suppression promotes neoplastic transformation, establishing it as a candidate tumor suppressor. Subtractive hybridization/GSE cloning; transfection overexpression and antisense chronic expression assays in cell lines Nature genetics Medium 8944021
1997 p33ING1 protein localizes to the nucleus, consistent with its role as a growth regulator. Indirect immunofluorescence; fluorescence in situ hybridization for chromosomal localization Cytogenetics and cell genetics Medium 9186514
1997 ING1 RNA and protein levels are 8–10-fold higher in senescent human diploid fibroblasts than in young cells; chronic antisense ING1 expression extends the proliferative lifespan by ~7 population doublings, establishing ING1 as a regulator of cellular senescence. Quantitative RT-PCR/Western blot; antisense chronic expression with proliferative lifespan measurement Molecular and cellular biology Medium 9121449
1997 p33ING1 promotes apoptosis: its levels increase upon apoptosis induction, overexpression enhances serum starvation-induced apoptosis synergistically with Myc, and antisense ING1 protects cells from apoptosis. Tetracycline-controlled c-myc system; antisense ING1 stable expression; apoptosis assays in P19 and fibroblast cells Cancer research Medium 9102209
1998 p33ING1 physically associates with p53 by co-immunoprecipitation, and the biological growth-inhibitory effects of ING1 require active p53; ING1 cooperates with p53 to activate transcription from the p21/WAF1 promoter. Co-immunoprecipitation; p21/WAF1 promoter-luciferase reporter assays; antisense/dominant-negative suppression epistasis Nature High 9440695
1999 The longer mouse ing1 isoform (p47 equivalent) forms a detectable complex with p53 by immunoprecipitation and interferes with p53 protein accumulation and p53-responsive promoter activation after DNA damage, while the shorter isoform (p33 equivalent) activates p53 responses — demonstrating that a single locus encodes both p53-suppressing and p53-activating proteins. Co-immunoprecipitation; p53-responsive promoter-reporter assays; Western blot after DNA damage The Journal of biological chemistry Medium 10542254
2000 Three yeast ING1 homologs (Yng1, Yng2, Pho23) co-immunoprecipitate with histone acetyltransferase (HAT) activity; Yng2 interacts with Tra1 (a NuA4 HAT complex component) by yeast two-hybrid and Co-IP, linking ING1-family proteins to HAT complexes and chromatin remodeling. Yeast two-hybrid; co-immunoprecipitation; HAT activity assays; yeast genetics (deletion phenotypes rescued by human ING1) Molecular and cellular biology High 10805724
2000 p33ING1b (but not p24ING1c) associates with the mSin3 transcriptional corepressor complex including Sin3, SAP30, HDAC1, and RbAp48; ING1 immune complexes deacetylate core histones in vitro; p33ING1b is functionally associated with HDAC1-mediated transcriptional repression. Co-immunoprecipitation; in vitro histone deacetylase assay; transcriptional repression reporter assays The Journal of biological chemistry High 11118440
2001 UV irradiation rapidly induces p33ING1b to bind PCNA through a PCNA-interacting protein (PIP) domain; PIP mutants that cannot bind PCNA fail to induce apoptosis and instead protect cells from UV-induced apoptosis, establishing that ING1-PCNA interaction is required for UV-induced programmed cell death. Co-immunoprecipitation; PIP domain mutagenesis; apoptosis assays after UV; competitive inhibition by p21 overexpression Journal of cell science High 11682605
2001 UV irradiation induces nucleolar translocation of ING1 proteins; ING1 contains two distinct 4-amino-acid nucleolar targeting sequences (NTS); NTS mutants that fail to translocate to the nucleolus do not efficiently induce apoptosis and instead protect cells from UV-induced apoptosis. Live-cell imaging with GFP fusions; NTS deletion/point mutants; apoptosis assays; fluorescence microscopy Nucleic acids research High 11353074
2001 p33ING1b (ING1) enhances repair of UV-damaged DNA and physically interacts with GADD45; this DNA repair function requires p53. Host-cell-reactivation DNA repair assay; co-immunoprecipitation of ING1 and GADD45; overexpression/antisense experiments Cancer research Medium 11431327
2001 Yng2p (yeast ING1 homolog) is a stable stoichiometric subunit of the NuA4 HAT complex; NuA4 from Δyng2 cells shows weak HAT activity; Yng2 PHD finger is required for full expression of p53-responsive genes and targeted NuA4-dependent histone H4 hyperacetylation. Mass spectrometry; immunoblotting; immunoprecipitation of purified NuA4; in vitro p53 interaction; histone acetylation assays in yeast Molecular and cellular biology High 11604499
2002 p33ING1b, but not p47ING1a, interacts with HAT-associated proteins (TRRAP, PCAF, CBP, p300) and induces hyperacetylation of histones H3 and H4 in vitro and in vivo; p47ING1a inhibits histone acetylation and binds HDAC1; p33ING1b affects the PCNA-p300 physical association. Co-immunoprecipitation; in vitro HAT assays; in vivo single-cell histone acetylation imaging; Western blot The Journal of biological chemistry High 12015309
2002 p33ING1b associates with the Sin3-HDAC complex through direct interaction between its N-terminal domain and SAP30; two distinct Sin3-p33ING1b complexes exist, one of which additionally contains Brg1-based SWI/SNF subunits; growth suppression by p33ING1b requires the intact Sin3-HDAC-interacting domain. Co-immunoprecipitation; biochemical complex purification; domain deletion/interaction mapping; growth suppression assays Molecular and cellular biology High 11784859
2003 p33ING1b represses AFP promoter transcription by binding AT-motifs and excluding HNF1, and also by physically interacting with hSIR2 (SIRT1) to inhibit its deacetylase activity, thereby increasing acetylation of p53 at Lys373/382 and enhancing p53-dependent transcription. Electrophoretic mobility shift assay (EMSA); promoter-reporter assays; co-immunoprecipitation; p53 acetylation Western blot Cancer research Medium 14522900
2005 p33ING1b contains two autonomous transcriptional silencing domains: an N-terminal domain whose silencing is HDAC-dependent (sensitive to TSA) and a C-terminal domain whose silencing is HDAC-independent (TSA-resistant); oncogenic Ras enhances ING1-mediated silencing through the MAP kinase pathway. Transcriptional reporter assays with deletion mutants; TSA and MAP kinase inhibitor treatment; colony formation assays; thymidine incorporation Molecular and cellular biology Medium 15601862
2006 p33ING1b interacts with 14-3-3 family proteins in a phosphorylation-dependent manner, causing significant cytoplasmic tethering of ING1b; overexpression of 14-3-3 inhibits ING1b-mediated induction of p21WAF1 after UV damage, demonstrating that subcellular mislocalization blocks ING1 biological activity. Co-immunoprecipitation; phosphatase treatment; subcellular fractionation; p21WAF1 Western blot; bioinformatics NLS/14-3-3 motif analysis Molecular and cellular biology Medium 16581770
2006 ARF physically interacts with p33ING1 in vivo, displaces ING1 from nuclear to nucleolar localization, and ARF-deficient primary fibroblasts show impaired ING1-mediated cell cycle arrest and p21CIP1/Mdm2 induction. Co-immunoprecipitation in vivo; fluorescence microscopy; ARF knockout MEFs; cell cycle analysis Oncogene Medium 16607280
2007 Phosphorylation of p33ING1b at Ser-126 stabilizes the protein; Chk1 phosphorylates Ser-126 predominantly upon DNA damage while Cdk1 does so under basal conditions; mutation of Ser-126 to Ala dramatically shortens ING1b half-life and alters cyclin B1 expression and melanoma cell proliferation. In vitro kinase assays with Chk1 and Cdk1; pulse-chase/half-life measurement; Ser126Ala mutagenesis; cyclin B1 Western blot; proliferation assays FASEB journal High 17585055
2007 Ing1-deficient mouse embryonic fibroblasts show defective senescence-like antiproliferative response to oncogenic Ras, reduced p53 protein stability, and impaired heterochromatin formation during oncogene-induced senescence. Ing1 knockout MEFs; oncogenic Ras expression; p53 stability assays; heterochromatin mark immunostaining; senescence assays The Journal of biological chemistry Medium 17693408
2007 p37Ing1 (mouse ING1) suppresses cell proliferation in a p53-independent manner; loss of p37Ing1 induces Bax expression and increases DNA damage-induced apoptosis irrespective of p53 status; p37Ing1 suppresses spontaneous follicular B-cell lymphomas in mice. p37Ing1 knockout mice; proliferation assays in p53 wild-type and p53-null backgrounds; Bax Western blot; tumor incidence monitoring Cancer research Medium 17332334
2008 The ING1 PHD finger binds histone H3 trimethylated at Lys4 (H3K4me3) but not other histone modifications; a 2.1 Å crystal structure reveals that Y212 and W235 form a hydrophobic pocket making cation-π contacts with the trimethylammonium group; W235A and cancer-associated mutations (N216S, V218I, G221V) disrupt H3K4me3 binding and abolish ING1's ability to stimulate DNA repair and promote apoptosis. Peptide microarray; X-ray crystallography (2.1 Å); site-directed mutagenesis; UV-induced DNA repair assay (host-cell reactivation); apoptosis assays in stable melanoma cell clones Journal of molecular biology High 18533182
2008 ING1 proteins contain a lamin interaction domain (LID) through which they bind and colocalize with lamin A; LMNA-/- cells show reduced ING1 levels and ING1 mislocalization; ectopic lamin A re-targets ING1 to the nucleus; ING1 lacking the LID does not interact with lamin A and cannot affect apoptosis. Co-immunoprecipitation; lamin A knockout cells; ectopic lamin A expression; GFP-ING1 localization imaging; LID deletion mutagenesis; apoptosis assays Nature cell biology High 18836436
2008 p33ING1b interacts with nuclear import machinery (karyopherins alpha2 and beta1) through basic NLS sequences adjacent to its PHD domain; deletion of NLS motifs prevents complete nuclear localization and abolishes ING1b-induced p21WAF1 expression. Co-immunoprecipitation; NLS deletion mutagenesis; subcellular localization imaging; p21WAF1 Western blot Biochemical and biophysical research communications Medium 18655775
2008 p33ING1b is degraded by the 20S proteasome; NQO1 inhibits its proteasomal degradation; UV irradiation induces phosphorylation at Ser-126, which facilitates ING1b interaction with NQO1 and thereby stabilizes the protein. Proteasome inhibitors; partial proteasome complex isolation; in vitro degradation assays; in vitro interaction assays; NQO1 co-immunoprecipitation EMBO reports High 18388957
2010 ING1 binds to the DGCR8 promoter and represses its transcription through chromatin regulation; ING1 and DGCR8 cooperate to restrain cell proliferation. Genome-wide expression microarray in Ing1-null MEFs; chromatin immunoprecipitation (ChIP) at DGCR8 promoter; proliferation assays Cancer research Medium 20179197
2010 p33ING1b triggers cellular senescence in a p53-dependent manner in human primary fibroblasts; endogenous ING1 accumulates in chromatin in oncogene-induced senescent cells; recognition of H3K4me3 by the PHD finger is required for ING1-induced senescence; a tumor-derived ING1 mutant fails to induce senescence. RNAi knockdown; PHD-finger point mutants; oncogene-induced senescence assays; chromatin fractionation; gene expression profiling Aging cell Medium 21078114
2011 ING1 stabilizes wild-type p53 by blocking its polyubiquitination; ING1 contains a ubiquitin-binding domain (UBD) overlapping its polybasic region (PBR) that binds ubiquitin with high affinity (Kd ~100 nM); ING1 physically interacts with the deubiquitinase HAUSP; knockdown of HAUSP blocks ING1-mediated p53 stabilization. Ubiquitin-binding assays; co-immunoprecipitation of ING1-HAUSP; p53 ubiquitination Western blots; ING1 knockdown; affinity binding measurements PloS one Medium 21731648
2011 p33ING1b upregulates p16INK4a transcription to induce cellular senescence; p33ING1b and the HAT p300 bind to the p16INK4a promoter; the p300/CBP inhibitor curcumin reverses p16INK4a induction by p33ING1b. Overexpression; RT-PCR/Western blot for p16; chromatin immunoprecipitation (ChIP); pharmacological inhibition FEBS letters Medium 21896275
2012 After UV irradiation, p33ING1 translocates into the nucleolus and binds the nucleolar protein CSIG; this interaction requires ING1's nucleolar targeting sequence; ING1 enhances CSIG protein stability; the ING1-CSIG complex promotes apoptosis via Bax activation. Co-immunoprecipitation; fluorescence microscopy; UV irradiation; Western blot for CSIG stability; apoptosis assays Cell death & disease Medium 22419112
2013 ING1 (Ing1) is required for targeting active DNA demethylation by recruiting the DNA demethylation regulator Gadd45a to H3K4me3-marked chromatin; reduced H3K4 methylation impairs Gadd45a/Ing1 recruitment and gene-specific DNA demethylation. Xenopus laevis model; Ing1 knockdown; Gadd45a recruitment assays; DNA methylation analysis; H3K4me3 ChIP Genes & development Medium 23388825
2013 ING1 translocates to the mitochondria in response to apoptosis-inducing stimuli independently of p53; endogenous ING1 physically interacts with BAX and colocalizes with BAX upon UV in a UV-inducible manner; mitochondria-targeted ING1 induces apoptosis more efficiently than wild-type ING1; ING1 contains a BH3-like domain. Subcellular fractionation; co-immunoprecipitation of ING1 and BAX; mitochondria-targeted ING1 construct; apoptosis assays in multiple breast cancer cell lines; immunofluorescence colocalization Cell death & disease Medium 24008732
2013 Src tyrosine kinase physically associates with and phosphorylates ING1 both in vitro and in vivo, causing nuclear-to-cytoplasmic relocalization and decreased ING1 stability; Src antagonizes ING1-induced apoptosis through both kinase-dependent and kinase-independent mechanisms. In vitro kinase assay; co-immunoprecipitation; subcellular localization imaging; apoptosis assays; kinase-dead Src controls PloS one Medium 23585863
2017 ING1b binds rDNA chromatin, recruits HDAC1 to rDNA loci, increases association of rDNA with the NoRC repressor complex, deacetylates active histone marks H3K9 and H3K27 on rDNA, and thereby represses rRNA/rDNA transcription; loss of ING1 enhances nucleolar localization of phospho-mTOR and its association with Raptor and GβL; ING1 inhibits UBF activity and the UBF-mTOR interaction. ChIP of ING1, HDAC1, NoRC, H3K9ac, H3K27ac at rDNA; co-immunoprecipitation; rRNA quantification; mTOR localization imaging; knockdown experiments Nucleic acids research Medium 27903908
2002 Mouse ING1 homolog (mINGh) physically interacts with the anti-apoptotic protein A1/Bfl-1 (identified by yeast two-hybrid); mINGh enhances cell death in mammary epithelial cells and this effect is inhibited by A1, placing ING1 in a functional antagonism with A1 in apoptosis regulation. Yeast two-hybrid screen; apoptosis assays in HC11 mammary epithelial cells; A1 overexpression co-transfection Cancer research Low 11888890
2005 The PCNA-associated protein p15PAF interacts with p33ING1b in the same complex in cell cultures; this interaction is detected by co-immunoprecipitation and both proteins show UV-enhanced association. Co-immunoprecipitation; immunofluorescence colocalization Experimental cell research Low 16288740
2003 p33ING1b weakly physically associates with estrogen receptor alpha (ERα) in vitro and enhances estrogen-induced ERα transcriptional activity through the AF2 domain of ERα, acting as a coactivator. In vitro translated protein interaction assay; ERα transcriptional reporter assays; AF2 deletion mutant analysis The Journal of steroid biochemistry and molecular biology Low 14630091
2021 ING1 and ING2 are recruited to a negative androgen response element (nARE) in the hTERT promoter in an androgen-dependent manner and mediate AR-regulated transcriptional repression of hTERT; ING1 and ING2 knockdown impairs this repression. Chromatin immunoprecipitation (ChIP); promoter-reporter assays; siRNA knockdown; ex vivo patient samples Cancers Medium 34439179

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Suppression of the novel growth inhibitor p33ING1 promotes neoplastic transformation. Nature genetics 266 8944021
1998 The candidate tumour suppressor p33ING1 cooperates with p53 in cell growth control. Nature 263 9440695
2002 Role of the Sin3-histone deacetylase complex in growth regulation by the candidate tumor suppressor p33(ING1). Molecular and cellular biology 192 11784859
2002 Different HATS of the ING1 gene family. Trends in cell biology 149 12446115
2001 UV-induced binding of ING1 to PCNA regulates the induction of apoptosis. Journal of cell science 141 11682605
2000 Three yeast proteins related to the human candidate tumor suppressor p33(ING1) are associated with histone acetyltransferase activities. Molecular and cellular biology 141 10805724
1997 A novel candidate tumor suppressor, ING1, is involved in the regulation of apoptosis. Cancer research 141 9102209
1997 Extension of the replicative life span of human diploid fibroblasts by inhibition of the p33ING1 candidate tumor suppressor. Molecular and cellular biology 136 9121449
2000 Genomic structure of the human ING1 gene and tumor-specific mutations detected in head and neck squamous cell carcinomas. Cancer research 131 10866301
1999 Suppression of ING1 expression in sporadic breast cancer. Oncogene 124 10498868
2000 Differential association of products of alternative transcripts of the candidate tumor suppressor ING1 with the mSin3/HDAC1 transcriptional corepressor complex. The Journal of biological chemistry 119 11118440
2008 Histone H3K4me3 binding is required for the DNA repair and apoptotic activities of ING1 tumor suppressor. Journal of molecular biology 111 18533182
2002 Human ING1 proteins differentially regulate histone acetylation. The Journal of biological chemistry 104 12015309
2001 UV induces nucleolar translocation of ING1 through two distinct nucleolar targeting sequences. Nucleic acids research 103 11353074
2001 The tumor suppressor candidate p33(ING1) mediates repair of UV-damaged DNA. Cancer research 99 11431327
1999 Cancer-testis antigens and ING1 tumor suppressor gene product are breast cancer antigens: characterization of tissue-specific ING1 transcripts and a homologue gene. Cancer research 97 10626813
2003 ING1 represses transcription by direct DNA binding and through effects on p53. Cancer research 93 14522900
2001 Role of an ING1 growth regulator in transcriptional activation and targeted histone acetylation by the NuA4 complex. Molecular and cellular biology 91 11604499
1999 Adenovirus-mediated transfer of p33ING1 with p53 drastically augments apoptosis in gliomas. Cancer research 88 10554029
2008 Tethering by lamin A stabilizes and targets the ING1 tumour suppressor. Nature cell biology 79 18836436
2001 Genetic alterations of candidate tumor suppressor ING1 in human esophageal squamous cell cancer. Cancer research 78 11389058
1999 Reduced expression of p33(ING1) and the relationship with p53 expression in human gastric cancer. Cancer letters 77 10660101
2007 Deletion of p37Ing1 in mice reveals a p53-independent role for Ing1 in the suppression of cell proliferation, apoptosis, and tumorigenesis. Cancer research 73 17332334
2008 NAD(P)H quinone oxidoreductase 1 inhibits the proteasomal degradation of the tumour suppressor p33(ING1b). EMBO reports 68 18388957
1997 Cellular localization and chromosome mapping of a novel candidate tumor suppressor gene (ING1). Cytogenetics and cell genetics 66 9186514
2011 Down-regulation of miR-622 in gastric cancer promotes cellular invasion and tumor metastasis by targeting ING1 gene. World journal of gastroenterology 62 21528065
1999 Structure and regulation of the mouse ing1 gene. Three alternative transcripts encode two phd finger proteins that have opposite effects on p53 function. The Journal of biological chemistry 62 10542254
1998 Cloning of a novel gene (ING1L) homologous to ING1, a candidate tumor suppressor. Cytogenetics and cell genetics 62 10072587
2006 Targeted disruption of the mouse ing1 locus results in reduced body size, hypersensitivity to radiation and elevated incidence of lymphomas. Oncogene 61 16170338
2002 ING1 isoforms differentially affect apoptosis in a cell age-dependent manner. Cancer research 61 12154053
1999 Decreased expression of p33ING1 mRNA in lymphoid malignancies. American journal of hematology 61 10577281
2004 ING-1, a monoclonal antibody targeting Ep-CAM in patients with advanced adenocarcinomas. Clinical cancer research : an official journal of the American Association for Cancer Research 58 15569986
2005 The PCNA-associated factor KIAA0101/p15(PAF) binds the potential tumor suppressor product p33ING1b. Experimental cell research 54 16288740
2000 Diminished expression of ING1 mRNA and the correlation with p53 expression in breast cancers. Cancer letters 53 10754201
2013 ING1 and ING2: multifaceted tumor suppressor genes. Cellular and molecular life sciences : CMLS 52 23412501
2002 p33(ING1) enhances UVB-induced apoptosis in melanoma cells. Experimental cell research 51 12243754
2006 Subcellular targeting of p33ING1b by phosphorylation-dependent 14-3-3 binding regulates p21WAF1 expression. Molecular and cellular biology 50 16581770
2000 p24/ING1-ALT1 and p47/ING1-ALT2, distinct alternative transcripts of p33/ING1. Journal of human genetics 48 10807544
2018 Nitazoxanide, an antiprotozoal drug, inhibits late-stage autophagy and promotes ING1-induced cell cycle arrest in glioblastoma. Cell death & disease 47 30302016
2000 Molecular analysis of the candidate tumor suppressor gene ING1 in human head and neck tumors with 13q deletions. Genes, chromosomes & cancer 47 10679922
2003 Altered subcellular localization and low frequency of mutations of ING1 in human brain tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 45 14676120
2000 Expression of the novel tumour suppressor p33(ING1)is independent of p53. British journal of cancer 44 11076655
2005 Growth inhibition by the tumor suppressor p33ING1 in immortalized and primary cells: involvement of two silencing domains and effect of Ras. Molecular and cellular biology 43 15601862
2001 The tumor suppressor ING1: structure and function. Experimental cell research 43 11461112
2013 Ing1 functions in DNA demethylation by directing Gadd45a to H3K4me3. Genes & development 42 23388825
2002 Identification of the p33(ING1)-regulated genes that include cyclin B1 and proto-oncogene DEK by using cDNA microarray in a mouse mammary epithelial cell line NMuMG. Cancer research 42 11956069
2007 Phosphorylation of the tumor suppressor p33(ING1b) at Ser-126 influences its protein stability and proliferation of melanoma cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 41 17585055
2002 Facilitation of adenoviral wild-type p53-induced apoptotic cell death by overexpression of p33(ING1) in T.Tn human esophageal carcinoma cells. Oncogene 41 11850840
2005 Epigenetic and genetic alterations of p33ING1b in ovarian cancer. Carcinogenesis 39 15677627
2011 The p53 tumor suppressor is stabilized by inhibitor of growth 1 (ING1) by blocking polyubiquitination. PloS one 37 21731648
2006 Alterations in novel candidate tumor suppressor genes, ING1 and ING2 in human lung cancer. Oncology reports 36 16465410
2002 Loss of nuclear expression of the p33(ING1b) inhibitor of growth protein in childhood acute lymphoblastic leukaemia. Journal of clinical pathology 36 12147653
2002 Nuclear to cytoplasmic compartment shift of the p33ING1b tumour suppressor protein is associated with malignancy in melanocytic lesions. Histopathology 35 11943021
2003 Downregulation of nuclear expression of the p33(ING1b) inhibitor of growth protein in invasive carcinoma of the breast. Journal of clinical pathology 34 12835295
1997 Localization of the candidate tumor suppressor gene ING1 to human chromosome 13q34. Somatic cell and molecular genetics 34 9330636
2004 Mutations of the ING1 tumor suppressor gene detected in human melanoma abrogate nucleotide excision repair. International journal of oncology 33 15201991
2002 Comparative assessment expression of the inhibitor of growth 1 gene (ING1) in normal and neoplastic tissues. Hybridoma and hybridomics 33 11991811
2013 ING1 induces apoptosis through direct effects at the mitochondria. Cell death & disease 31 24008732
2011 The expression of p33(ING1), p53, and autophagy-related gene Beclin1 in patients with non-small cell lung cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 30 21779982
2010 Regulation of the microRNA processor DGCR8 by the tumor suppressor ING1. Cancer research 30 20179197
2010 The tumor suppressor ING1 contributes to epigenetic control of cellular senescence. Aging cell 30 21078114
2006 A functional link between the tumour suppressors ARF and p33ING1. Oncogene 30 16607280
2012 ING1 and 5-azacytidine act synergistically to block breast cancer cell growth. PloS one 29 22916295
2003 Analyses of the tumour suppressor ING1 expression and gene mutation in human basal cell carcinoma. International journal of oncology 29 12632089
2002 The novel tumour suppressor gene ING1 is overexpressed in human melanoma cell lines. The British journal of dermatology 29 11966686
2002 Expression of p33(ING1) in hepatocellular carcinoma: relationships to tumour differentiation and cyclin E kinase activity. Scandinavian journal of gastroenterology 29 12523595
2007 Ing1 mediates p53 accumulation and chromatin modification in response to oncogenic stress. The Journal of biological chemistry 27 17693408
2007 Pharmacokinetic and safety study of subcutaneously administered weekly ING-1, a human engineere monoclonal antibody targeting human EpCAM, in patients with advanced solid tumors. Annals of oncology : official journal of the European Society for Medical Oncology 27 17693421
2004 No ING1 mutations in human brain tumours but reduced expression in high malignancy grades of astrocytoma. International journal of cancer 27 14961591
2000 A panel of CAb antibodies recognize endogenous and ectopically expressed ING1 protein. Hybridoma 27 10868796
1999 The candidate tumour suppressor gene, ING1, is retained in colorectal carcinomas. European journal of cancer (Oxford, England : 1990) 27 10615239
2012 Nucleolar protein CSIG is required for p33ING1 function in UV-induced apoptosis. Cell death & disease 25 22419112
2003 Expression of p33ING1 mRNA and chemosensitivity in brain tumor cells. Anticancer research 25 12820433
2011 The tumor suppressor p33ING1b upregulates p16INK4a expression and induces cellular senescence. FEBS letters 24 21896275
2015 MicroRNA let-7b suppresses human gastric cancer malignancy by targeting ING1. Cancer gene therapy 23 25613480
2005 Inhibitory effect of tumor suppressor p33(ING1b) and its synergy with p53 gene in hepatocellular carcinoma. World journal of gastroenterology 22 15800978
2018 Down-regulation of miR-500 and miR-628 suppress non-small cell lung cancer proliferation, migration and invasion by targeting ING1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 30372865
2013 Src regulates the activity of the ING1 tumor suppressor. PloS one 20 23585863
2008 ING1 protein targeting to the nucleus by karyopherins is necessary for activation of p21. Biochemical and biophysical research communications 20 18655775
2004 Dysfunction of p53 pathway in human colorectal cancer: analysis of p53 gene mutation and the expression of the p53-associated factors p14ARF, p33ING1, p21WAF1 and MDM2. International journal of oncology 20 15375540
2003 ING1 and p53 tumor suppressor gene alterations in adenocarcinomas of the esophagogastric junction. Cancer letters 20 12637159
2001 Mutational analysis of the candidate tumor suppressor gene ING1 in Indian oral squamous cell carcinoma. Oral oncology 20 11287275
2016 A novel crosstalk between the tumor suppressors ING1 and ING2 regulates androgen receptor signaling. Journal of molecular medicine (Berlin, Germany) 19 27305909
2002 Expression and sequence analyses of p33(ING1) gene in myeloid leukemia. American journal of hematology 19 11835353
2017 ING1 regulates rRNA levels by altering nucleolar chromatin structure and mTOR localization. Nucleic acids research 18 27903908
2021 Antithetic hTERT Regulation by Androgens in Prostate Cancer Cells: hTERT Inhibition Is Mediated by the ING1 and ING2 Tumor Suppressors. Cancers 17 34439179
2005 Multiple variants of the ING1 and ING2 tumor suppressors are differentially expressed and thyroid hormone-responsive in Xenopus laevis. General and comparative endocrinology 17 15955533
2005 The p33ING1b tumor suppressor cooperates with p53 to induce apoptosis in response to etoposide in human osteosarcoma cells. Life sciences 16 16325212
1997 Specific monoclonal antibody raised against the p33ING1 tumor suppressor. Hybridoma 16 9455706
2007 Nuclear to cytoplasmic shift of p33(ING1b) protein from normal oral mucosa to oral squamous cell carcinoma in relation to clinicopathological variables. Journal of cancer research and clinical oncology 15 17805569
2004 Genetic alterations and reduced expression of tumor suppressor p33(ING1b) in human exocrine pancreatic carcinoma. World journal of gastroenterology 15 15534913
2003 p33(ING1b) stimulates the transcriptional activity of the estrogen receptor alpha via its activation function (AF) 2 domain. The Journal of steroid biochemistry and molecular biology 15 14630091
2010 The inhibitor of growth 1 (ING1) is involved in trichostatin A-induced apoptosis and caspase 3 signaling in p53-deficient glioblastoma cells. Oncology research 14 20681406
2005 The tumor suppressor p33ING1b enhances taxol-induced apoptosis by p53-dependent pathway in human osteosarcoma U2OS cells. Cancer biology & therapy 14 15662138
2014 Reduced ING1 levels in breast cancer promotes metastasis. Oncotarget 13 24962136
2002 Mouse ING1 homologue, a protein interacting with A1, enhances cell death and is inhibited by A1 in mammary epithelial cells. Cancer research 13 11888890
2009 The inhibitor of growth 1 (ING1) proteins suppress angiogenesis and differentially regulate angiopoietin expression in glioblastoma cells. Oncology research 12 20066899
2007 Down-regulation of the inhibitor of growth 1 (ING1) tumor suppressor sensitizes p53-deficient glioblastoma cells to cisplatin-induced cell death. Journal of neuro-oncology 12 17763999
2007 The predictive value of p53 and p33(ING1b) in patients with Dukes'C colorectal cancer. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland 12 17949449
2011 Genetic alterations of tumor suppressor ING1 in human non-small cell lung cancer. Oncology reports 11 21286670

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