HCSGD entry for ING1
1. General information
| Official gene symbol | ING1 |
|---|---|
| Entrez ID | 3621 |
| Gene full name | inhibitor of growth family, member 1 |
| Other gene symbols | p24ING1c p33 p33ING1 p33ING1b p47 p47ING1a |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005634 | Nucleus | NAS | cellular_component |
| GO:0006606 | Protein import into nucleus | IEA | biological_process |
| GO:0007049 | Cell cycle | IEA | biological_process |
| GO:0008270 | Zinc ion binding | IEA | molecular_function |
| GO:0008285 | Negative regulation of cell proliferation | TAS | biological_process |
| GO:0010941 | Regulation of cell death | IEA | biological_process |
| GO:0030308 | Negative regulation of cell growth | NAS | biological_process |
| GO:0035064 | Methylated histone residue binding | IDA | molecular_function |
| GO:0045893 | Positive regulation of transcription, DNA-templated | IEA | biological_process |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.7756968200 | 0.4169370427 | 0.9999902473 | 1.0000000000 |
- Individual experiment result
( "-" represent NA in the specific microarray platform )
( "-" represent NA in the specific microarray platform )
| Data source | Up or down | Log fold change |
|---|---|---|
| GSE11954 | Up | 0.0599918122 |
| GSE13712_SHEAR | Down | -0.0670800036 |
| GSE13712_STATIC | Down | -0.2741430070 |
| GSE19018 | Up | 0.0750575118 |
| GSE19899_A1 | Up | 0.0633056537 |
| GSE19899_A2 | Down | -0.1475205257 |
| PubMed_21979375_A1 | Up | 0.5094820305 |
| PubMed_21979375_A2 | Down | -0.1080597434 |
| GSE35957 | Down | -0.7609812006 |
| GSE36640 | Down | -0.4911837394 |
| GSE54402 | Up | 0.0997922330 |
| GSE9593 | Down | -0.2328894772 |
| GSE43922 | Up | 0.0542823987 |
| GSE24585 | Up | 0.4221995664 |
| GSE37065 | Down | -0.0779488647 |
| GSE28863_A1 | Up | 0.0294456888 |
| GSE28863_A2 | Down | -0.0562873493 |
| GSE28863_A3 | Up | 0.2128324312 |
| GSE28863_A4 | Up | 0.0292447366 |
| GSE48662 | Down | -0.1742623764 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
Not regulated by compounds
- Drugs
Not regulated by drugs
- MicroRNAs
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-662 | MIMAT0003325 | MIRT006996 | Luciferase reporter assay | Functional MTI | 21528065 |
| hsa-miR-103a-3p | MIMAT0000101 | MIRT026987 | Sequencing | Functional MTI (Weak) | 20371350 |
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- mirRecord
MicroRNA name | mirBase ID | Target site number | MiRNA mature ID | Test method inter | MiRNA regulation site | Reporter target site | Pubmed ID |
|---|---|---|---|---|---|---|---|
| hsa-miR-622 | MIMAT0003291 | 1 | hsa-miR-622 | {Western blot} | {overexpression by miRNA precursor transfection} | 21528065 |
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6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 24 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 27305909 | A novel crosstalk between the tumor suppressors ING1 and ING2 regulates androgen receptor signaling |
| 27305909 | Inhibitor of growth 1 (ING1) and ING2 are tumor suppressors with reduced expression in many cancer types |
| 27305909 | There are also indications of misregulation of ING1 and ING2 in PCa |
| 27305909 | However, the roles of ING1 and ING2 in PCa and AR signaling are poorly understood |
| 27305909 | This is associated with growth reduction of LNCaP cells by ING1 KD |
| 27305909 | In line with this, using Ing1 knockout (KO) mice, we provide further evidence that ING1 deficiency downregulates prostate-specific AR target genes in vivo |
| 27305909 | The unexpected finding that the ING1 KD results in growth inhibition was further analyzed and can be explained by a compensatory mechanism through enhanced levels of ING2 protein in ING1-deficient condition |
| 27305909 | ING2 levels are increased upon downregulation of ING1 expression indicating a compensatory mechanism and suggests a novel crosstalk between ING1 and ING2 tumor suppressors to inhibit AR signaling and induce cellular senescence in PCa cells |
| 27305909 | KEY MESSAGE: * The tumor suppressors ING1 and 2 are dysregulated in human prostate cancer |
| 26993046 | Inhibitor of growth 1 (ING1) is a tumor suppressor that regulates various cellular processes including cell proliferation |
| 26993046 | Interestingly, ING1 expression is upregulated in senescent primary human prostate cells; however, its role in AR signaling in PCa was unknown |
| 24008732 | ING1 induces apoptosis through direct effects at the mitochondria |
| 24008732 | ING1 also interacts with members of the14-3-3 family leading to its cytoplasmic relocalization |
| 24008732 | Overexpression of ING1 enhances expression of the Bax gene and was reported to alter mitochondrial membrane potential in a p53-dependent manner |
| 24008732 | Here we show that ING1 translocates to the mitochondria of primary fibroblasts and established epithelial cell lines in response to apoptosis inducing stimuli, independent of the cellular p53 status |
| 24008732 | The ability of ING1 to induce apoptosis in various breast cancer cell lines correlates well with its degree of translocation to the mitochondria after UV treatment |
| 24008732 | Endogenous ING1 protein specifically interacts with the pro-apoptotic BCL2 family member BAX, and colocalizes with BAX in a UV-inducible manner |
| 24008732 | Ectopic expression of a mitochondria-targeted ING1 construct is more proficient in inducing apoptosis than the wild type ING1 protein |
| 24008732 | Also, sequence analysis of ING1 reveals the presence of a BH3-like domain |
| 24008732 | These data suggest a model in which stress-induced cytoplasmic relocalization of ING1 by14-3-3 induces ING1-BAX interaction to promote mitochondrial membrane permeability and represent a paradigm shift in our understanding of ING1 function in the cytoplasm and its contribution to apoptosis [corrected] |
| 23255913 | Cytoplasmic expression of p33(ING1b) is correlated with tumorigenesis and progression of human esophageal squamous cell carcinoma |
| 23255913 | Previous studies have shown that p33(ING1b) is involved in the restriction of cell growth and proliferation, apoptosis, tumor anchorage-independent growth, cellular senescence, maintenance of genomic stability and modulation of cell cycle checkpoints |
| 23255913 | Loss of nuclear p33(ING1b) has been observed in melanoma, seminoma, papillary thyroid carcinoma, oral squamous cell carcinoma, breast ductal cancer and acute lymphoblastic leukemia |
| 23255913 | Inactivation and/or decreased expression of p33(ING1b) have been reported in various types of cancer, including head and neck squamous cell, breast, lung, stomach, blood and brain malignancies |
| 23255913 | Since little is known about the clinicopathological significance of p33(ING1b) in esophageal squamous cell carcinoma (ESCC), this study aimed to investigate the association of p33(ING1b) expression with clinicopathological variables and particularly interesting new cysteine-histidine rich protein (PINCH) in patients with ESCC |
| 23255913 | The results revealed that the positive expression of p33(ING1b) protein in normal squamous cells was localized in the nucleus alone and the positive rate was 95%, while in ESCCs, the positive expression was mainly in the cytoplasm, together with nuclear expression, and the positive rate was 36% (P<0 |
| 23255913 | The cytoplasmic expression of p33(ING1b) was positively related to PINCH expression (P<0 |
| 22419112 | Nucleolar protein CSIG is required for p33ING1 function in UV-induced apoptosis |
| 22419112 | We identified p33ING1 as a binding partner that interacts with CSIG |
| 22419112 | After UV irradiation, p33ING1 increases its protein expression, translocates into the nucleolus and binds CSIG |
| 21896275 | The tumor suppressor p33ING1b upregulates p16INK4a expression and induces cellular senescence |
| 21896275 | ING1 protein is a tumor suppressor which plays significant roles in multiple cellular activities |
| 21896275 | Here we studied the functions of ING1 isoforms in cellular senescence and gene regulation, with focus on p16(INK4a) |
| 21896275 | We observe that p33(ING1b) protein is the major ING1 isoform expressed in 2BS human diploid fibroblasts |
| 21896275 | These results help to better understand the function of ING1 |
| 21767350 | The Inhibitor of Growth (ING) proteins represent a type II tumor suppressor family comprising five conserved genes, ING1 to ING5 |
| 21767350 | While ING1, ING2 and ING3 proteins are stable components of the mSIN3a-HDAC complexes, the association of ING1, ING4 and ING5 with HAT protein complexes was also reported |
| 21767350 | Among these the ING1 and ING2 have been analyzed more deeply |
| 21767350 | ING1 and ING2 are localized in the cell nucleus and associated with chromatin modifying enzymes, linking tumor suppression directly to chromatin regulation |
| 21767350 | In line with this, the expression of ING1 in tumors is aberrant or identified point mutations are mostly localized in the PHD finger and affect histone binding |
| 21767350 | Interestingly, ING1 protein levels increase in replicative senescent cells, latter representing an efficient pathway to inhibit cancer proliferation |
| 21767350 | In association with this, suppression of p33ING1 expression prolongs replicative life span and is also sufficient to bypass oncogene-induced senescence |
| 21767350 | Recent analyses of ING1- and ING2-deficient mice confirm a tumor suppressive role of ING1 and ING2 and also indicate an essential role of ING2 in meiosis |
| 21767350 | Here we summarize the activity of ING1 and ING2 as tumor suppressors, chromatin factors and in development |
| 21707358 | Domain recognition of the ING1 tumor suppressor by a panel of monoclonal antibodies |
| 21707358 | To better understand the functional attributes of the ING proteins, we have developed and further characterized a panel of monoclonal IgGs that we call CAbs 1-9 based on their recognition sites, strength of binding affinity, and their specificity for ING1 |
| 21707358 | All of the nine CAbs recognize the C-terminal half of the p33(ING1b) protein, which is fully conserved among all ING1 isoforms, being encoded by a common exon |
| 21707358 | Five of the nine CAbs recognized a fragment of ING1, which includes the NLS |
| 21707358 | The sequence between the LID and NLS is less conserved among the ING proteins and, as expected, CAbs 3 and 9 were completely specific for ING1 |
| 21176536 | OBJECTIVES: To investigate the pharmacological effects of azidothymidine (AZT) on p33ING1b expression, senescence and apoptosis of TJ905 glioblastoma cells |
| 21176536 | Semi-quantitative RT-PCR and cytochemical staining of senescence related-galactosidase (sbeta-Gal) were used to evaluate the expression of p33ING1b mRNA and to label the senescent cells at the 1st, 3rd and 6th generations, respectively |
| 21176536 | RESULTS: AZT induced the expression of p33ING1b mRNA and senescence of the tumor cells of the 1st generation in a dosage and time dependent manner |
| 21176536 | At the 6th generation, the relative amount of p33ING1b RT-PCR product (1 |
| 21176536 | There was a significant positive correlation between the p33ING1b mRNA expression and the labeling index of sbeta-Gal |
| 21078114 | The tumor suppressor ING1 contributes to epigenetic control of cellular senescence |
| 21078114 | Here, we have investigated the role of the p33ING1 tumor suppressor in the regulation of cellular senescence in human primary fibroblasts |
| 21078114 | We show that p33ING1 triggers a senescent phenotype in a p53-dependent fashion |
| 21078114 | Also, endogenous p33ING1 protein accumulates in chromatin in oncogene-senescent fibroblasts and its silencing by RNA interference impairs senescence triggered by oncogenes |
| 21078114 | Notably, the ability to induce senescence is lost in a mutant version of p33ING1 present in human tumors |
| 21078114 | Using specific point mutants, we further show that recognition of the chromatin mark H3K4me3 is essential for induction of senescence by p33ING1 |
| 21078114 | In summary, our results identify ING1 as a critical epigenetic regulator of cellular senescence in human fibroblasts and highlight its role in control of gene expression in the context of this tumor-protective response |
| 19442113 | Here, we review the evidence on the participation of ING proteins, mainly ING1 and ING2, in the implementation of the senescent response |
| 18801192 | RESULTS: We confirm the validity of this screen and show that ING1 interacts specifically with three of the three proteins tested; p38MAPK, MEKK4 and RAD50 |
| 18801192 | These novel ING-interacting proteins further link ING proteins to cell stress and DNA damage signaling, providing previously unknown upstream links to DNA damage response pathways in which ING1 participates |
| 18691180 | The major splicing isoforms of the ING1 locus are ING1a and INGlb |
| 18691180 | Here we show that alternative splicing of the ING1 message alters the INGla:INGlb ratio by approximately 30-fold in senescent compared to low passage primary fibroblasts |
| 18691180 | Gene expression appears to be altered by targeting of HDAC complexes to gene promoters since INGla associates with several-fold higher levels of HDAC1 in senescent, compared to replication-competent cells and ING1 is found on the PCNA promoter by chromatin immunoprecipitation analysis |
| 18691180 | These data demonstrate a novel role for the ING1 proteins in differentially regulating senescence-associated chromatin remodeling vs |
| 18513492 | Notably, also p33ING1 recruits HMT activity suggesting a more general biochemical interaction between members of p33ING family and HMT activity |
| 18193082 | In vitro and in vivo binding studies indicated that the p33(ING1b) and p33(ING2) subunits of the mSIN3A/HDAC1 complex are responsible for the recruitment of SIRT1 to the R2 domain |
| 15601862 | Growth inhibition by the tumor suppressor p33ING1 in immortalized and primary cells: involvement of two silencing domains and effect of Ras |
| 15601862 | ING1 was identified as an inhibitor of growth and has been described as a tumor suppressor |
| 15601862 | Furthermore, the expression of ING1 is induced in senescent cells and antisense ING1 extends the proliferative life span of primary human fibroblasts |
| 15601862 | Intriguingly, it has been shown that p33ING1 is associated with histone acetylation as well as with histone deacetylation function |
| 15601862 | Here we show that p33ING1 is a potent transcriptional silencer in various cell types |
| 15601862 | The amino (N)-terminal silencing domain is sensitive to the histone deacetylase inhibitor trichostatin A (TSA) whereas the carboxy-terminal silencing function is resistant to TSA, suggesting that p33ING1 confers gene silencing through both HDAC-dependent and -independent mechanisms |
| 15601862 | In addition, we show that both silencing domains of ING1 are involved in cell cycle control, as measured by inhibition of colony formation of immortalized cells and by thymidine incorporation of primary human diploid fibroblasts (HDF) |
| 15601862 | Interestingly, p33ING1 expression induces features of cellular senescence in HDFs |
| 15526165 | Early studies of the inhibitor of growth 1 ( ING1) gene, the founding member of the ING tumor suppressor family, demonstrated that this gene plays an important role in apoptosis and cellular senescence |
| 14522900 | ING1 represses transcription by direct DNA binding and through effects on p53 |
| 14522900 | The p47(ING1a) isoform also repressed AFP promoter activity, but in contrast to other ING isoforms, it repressed the p21(WAF1) promoter |
| 14522900 | Indeed, electrophoretic mobility shift assays confirmed that HNF1 binds to AT-motifs, but we found, surprisingly, that the ING1 complexes binding to these AT-motifs were devoid of HNF1 protein |
| 14522900 | Both ING1 and p53 were able to suppress AFP transcription and cause p21 induction; hSIR2, a negative regulator of the p53 protein, showed the opposite effects on the AFP promoter and, like HDAC1, repressed p21 promoter activity |
| 14522900 | In addition, we found that p33(ING1b) physically interacts with hSIR2, reverses its ability to induce the AFP promoter, and induces acetylation of p53 residues at Lys(373) and/or Lys(382) |
| 14522900 | These findings provide novel evidence that p33(ING1b) represses AFP transcription by at least two mechanisms, one of which includes p53 |
| 12835295 | Downregulation of nuclear expression of the p33(ING1b) inhibitor of growth protein in invasive carcinoma of the breast |
| 12835295 | BACKGROUND/AIMS: The inhibitor of growth gene 1 (ING1) is a modulator of cell cycle checkpoints, apoptosis, and cellular senescence |
| 12835295 | The most widely expressed ING1 isoform is p33(ING1b), which can modulate p53, a molecule that is frequently altered in breast cancer |
| 12835295 | Reduced ING1 mRNA expression has been observed in primary breast cancer expressing wild-type p53 |
| 12835295 | METHODS: p33(ING1b), p53, oestrogen receptor (ER), and progesterone receptor (PgR) expression was studied in 86 primary invasive breast cancers using immunohistochemistry |
| 12835295 | RESULTS: Reduced nuclear expression of p33(ING1b) was found in cancer cells, both in intensity and the proportion of cells staining |
| 12835295 | This was associated with enhanced cytoplasmic p33(ING1b) expression in a proportion of cases |
| 12835295 | These results provide evidence that p33(ING1b) alterations are associated with more poorly differentiated tumours |
| 12835295 | Positive correlations were found between nuclear p33(ING1b) expression and both ER and PgR expression |
| 12835295 | CONCLUSIONS: Optimum function of p53 is dependent on p33(ING1b) so that a reduction of nuclear p33(ING1b) expression, as seen in this series, would be predicted to compromise p53 function |
| 12835295 | This study showed that p33(ING1b) alterations were associated with more poorly differentiated tumours |
| 12835295 | Therefore, p33(ING1b) expression could be used as a marker of differentiation in invasive breast cancer |
| 12835295 | These results support the view that loss of p33(ING1b) may be an important molecular event in the differentiation and pathogenesis of invasive breast cancer |
| 12835293 | ING1 was the first to be identified and later isolated using an approach to detect genes whose expression is suppressed in cancer |
| 12835293 | Apart from the extensively studied ING1, little is known about the number of transcripts encoded by the other members or their gene structure |
| 12835293 | ING1 encodes several differentially spliced mRNAs, which may produce a family of proteins |
| 12835293 | ING1 gene mutation is uncommon in cancer, although the subcellular localisation of p33(INGb1) may have an effect on its function |
| 12154053 | ING1 isoforms differentially affect apoptosis in a cell age-dependent manner |
| 12154053 | Recently, several novel human ING1 isoforms have been cloned |
| 12154053 | We have examined the apoptotic effects and biochemical functions of the two major human ING1 isoforms p47(ING1a) and p33(ING1b) in young and senescent human diploid fibroblasts induced to enter into apoptosis by diverse treatments |
| 12154053 | We have found that ING1 displayed isoform-, stimulus- and cell age-dependent apoptotic properties |
| 12154053 | We present evidence indicating that ING1 proteins bind to chromatin and are regulated in a manner related to their apoptotic properties |
| 12154053 | This effect was accompanied by up-regulation of endogenous p33(ING1b) |
| 12154053 | Ectopic up-regulation of p33(ING1b), but not p47(ING1a), also induced apoptosis and sensitized young but not senescent cells to UV irradiation and hydrogen peroxide-mediated apoptosis |
| 12154053 | Cotransfection of p33(ING1b) and the tumor suppressor p53 increased the percentage of apoptotic cells yielded by either of these two proteins alone, in agreement with data from tumor cell models |
| 12154053 | Finally, we found that the chromatin binding affinity of p33(ING1b) was increased in senescent cells, which were resistant to apoptosis |
| 12154053 | Together, these data support the idea that the apoptotic functions of ING1 may be exerted by chromatin-related functions that are subject to cell age-dependent mechanisms of regulation |
| 9467719 | Identification and characterization of additional genes encoding growth inhibitors that are upregulated in senescent cells, such as the recently isolated p33ING1 protein, should provide a better understanding of the "aging program" that ceases to operate in the generation of immortal cancer cells |
| 9440695 | The candidate tumour suppressor p33ING1 cooperates with p53 in cell growth control |
| 9440695 | ING1 encodes a nuclear protein, p33ING1, overexpression of which inhibits growth of different cell lines |
| 9440695 | The properties of p33ING1 suggest its involvement in the negative regulation of cell proliferation and in the control of cellular ageing, anchorage dependence and apoptosis |
| 9440695 | Here we report that the biological effects of ING1 and p53 are interrelated and require the activity of both genes: neither of the two genes can, on its own, cause growth inhibition when the other one is suppressed |
| 9440695 | Furthermore, activation of transcription from the p21/WAF1 promoter, a key mechanism of p53-mediated growth control, depends on the expression of ING1 |
| 9440695 | A physical association between p33ING1 and p53 proteins has been detected by immunoprecipitation |
| 9440695 | These results indicate that p33ING1 is a component of the p53 signalling pathway that cooperates with p53 in the negative regulation of cell proliferation by modulating p53-dependent transcriptional activation |
| 9121449 | Extension of the replicative life span of human diploid fibroblasts by inhibition of the p33ING1 candidate tumor suppressor |
| 9121449 | We therefore studied the potential involvement of a novel growth inhibitor and candidate tumor suppressor gene called ING1, which we have cloned recently (I |
| 9121449 | Our results show that the RNA and protein levels of ING1 were 8- to 10-fold higher in senescent cells than in young, proliferation-competent human diploid fibroblasts |
| 9121449 | Expression of the nuclear p33ING1 protein was regulated during the cell cycle, reaching maximal levels during DNA synthesis |
| 9121449 | Chronic expression of antisense ING1 RNA reproducibly resulted in extension of the proliferative life span of normal human fibroblasts by approximately seven population doublings |
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