HCSGD entry for IFI16
1. General information
| Official gene symbol | IFI16 |
|---|---|
| Entrez ID | 3428 |
| Gene full name | interferon, gamma-inducible protein 16 |
| Other gene symbols | IFNGIP1 PYHIN2 |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0000122 | Negative regulation of transcription from RNA polymerase II promoter | IDA IMP | biological_process |
| GO:0001819 | Positive regulation of cytokine production | TAS | biological_process |
| GO:0002218 | Activation of innate immune response | IDA | biological_process |
| GO:0003690 | Double-stranded DNA binding | IDA | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005634 | Nucleus | IDA | cellular_component |
| GO:0005654 | Nucleoplasm | IDA | cellular_component |
| GO:0005730 | Nucleolus | IDA | cellular_component |
| GO:0005737 | Cytoplasm | IDA | cellular_component |
| GO:0005829 | Cytosol | TAS | cellular_component |
| GO:0006351 | Transcription, DNA-templated | IEA | biological_process |
| GO:0006914 | Autophagy | IEA | biological_process |
| GO:0006954 | Inflammatory response | IEA | biological_process |
| GO:0008134 | Transcription factor binding | IDA | molecular_function |
| GO:0008283 | Cell proliferation | NAS | biological_process |
| GO:0010506 | Regulation of autophagy | IEP | biological_process |
| GO:0016607 | Nuclear speck | IDA | cellular_component |
| GO:0030097 | Hemopoiesis | NAS | biological_process |
| GO:0030099 | Myeloid cell differentiation | NAS | biological_process |
| GO:0030224 | Monocyte differentiation | IDA | biological_process |
| GO:0032481 | Positive regulation of type I interferon production | TAS | biological_process |
| GO:0032731 | Positive regulation of interleukin-1 beta production | IDA | biological_process |
| GO:0042149 | Cellular response to glucose starvation | IDA | biological_process |
| GO:0042771 | Intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | IDA | biological_process |
| GO:0043392 | Negative regulation of DNA binding | IDA | biological_process |
| GO:0045071 | Negative regulation of viral genome replication | IDA | biological_process |
| GO:0045087 | Innate immune response | TAS | biological_process |
| GO:0045824 | Negative regulation of innate immune response | IDA | biological_process |
| GO:0045892 | Negative regulation of transcription, DNA-templated | IDA | biological_process |
| GO:0045944 | Positive regulation of transcription from RNA polymerase II promoter | IDA IMP | biological_process |
| GO:0051607 | Defense response to virus | IMP | biological_process |
| GO:0071479 | Cellular response to ionizing radiation | IDA | biological_process |
| GO:0072332 | Intrinsic apoptotic signaling pathway by p53 class mediator | IMP | biological_process |
| GO:0097202 | Activation of cysteine-type endopeptidase activity | IMP | biological_process |
| GO:2000117 | Negative regulation of cysteine-type endopeptidase activity | IDA | biological_process |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.0176026709 | 0.0908754075 | 0.3257398174 | 0.5731923317 |
- 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 | 0.2091713593 |
| GSE13712_SHEAR | Up | 0.5600302865 |
| GSE13712_STATIC | Up | 0.1027525107 |
| GSE19018 | Up | 0.9994974139 |
| GSE19899_A1 | Up | 0.6630920665 |
| GSE19899_A2 | Down | -0.1029552133 |
| PubMed_21979375_A1 | Down | -0.4425910742 |
| PubMed_21979375_A2 | Up | 0.4768508512 |
| GSE35957 | Down | -0.6684475514 |
| GSE36640 | Down | -0.5992634794 |
| GSE54402 | Up | 0.5219565291 |
| GSE9593 | Up | 0.1963801210 |
| GSE43922 | Down | -0.0809192298 |
| GSE24585 | Down | -1.1909222701 |
| GSE37065 | Up | 0.3785473781 |
| GSE28863_A1 | Up | 0.8695796100 |
| GSE28863_A2 | Up | 1.2139993580 |
| GSE28863_A3 | Down | -0.4622708831 |
| GSE28863_A4 | Down | -0.3744363753 |
| GSE48662 | Down | -0.5187463824 |
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-335-5p | MIMAT0000765 | MIRT017847 | Microarray | Functional MTI (Weak) | 18185580 |
| hsa-miR-124-3p | MIMAT0000422 | MIRT022657 | Proteomics;Microarray | Non-Functional MTI (Weak) | 18668037 |
| hsa-miR-98-5p | MIMAT0000096 | MIRT027519 | Microarray | Functional MTI (Weak) | 19088304 |
| hsa-miR-26b-5p | MIMAT0000083 | MIRT029441 | Microarray | Functional MTI (Weak) | 19088304 |
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- mirRecord
No target information from mirRecord
6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 9 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 27063514 | IFI16, an amplifier of DNA-damage response: Role in cellular senescence and aging-associated inflammatory diseases |
| 27063514 | DDR-induced signaling in cells activates the ATM-p53 and ATM-IKKalpha/beta-interferon (IFN)-beta signaling pathways, thus leading to an induction of the p53 and IFN-inducible IFI16 gene |
| 27063514 | Further, upon DNA-damage, DNA accumulates in the cytoplasm, thereby inducing the IFI16 protein and STING-dependent IFN-beta production and activation of the IFI16 inflammasome, resulting in the production of proinflammatory cytokines (e |
| 27063514 | Increased expression of IFI16 protein in a variety of cell-types promotes cellular senescence |
| 27063514 | Because expression of the IFI16 gene is induced by activation of DNA-damage response in cells and increased levels of IFI16 protein in cells potentiate the p53-mediated transcriptional activation of genes and p53 and pRb-mediated cell cycle arrest, we discuss how an improved understanding of the role of IFI16 protein in cellular senescence and associated inflammatory secretory phenotype is likely to identify the molecular mechanisms that contribute to the development of aging-associated human inflammatory diseases and a failure to cancer therapy |
| 24491427 | IFI16 mis-localization can be a contributing factor to hepatocellular carcinoma progression |
| 24491427 | Interferon-gamma inducible protein 16 (IFI16), a multifunctional protein, has roles in anti-proliferation, autophagy, cell senescence, anti-inflammation, and DNA sensor to trigger innate immunity |
| 24491427 | IFI16 physiologically absents in adult healthy hepatocyte, but exists in liver cancer cells |
| 24491427 | Interestingly, increasing evidences suggest that dysregulation or/and loss of IFI16 function have a critical role in drug resistance and tumor progression |
| 24491427 | In our study, to our knowledge, we first showed that IFI16 is a chromatin-binding protein in four HCC cell lines with different TP53 genotype, but not in fetal liver cell line, L02 cells |
| 21471287 | Differential roles for the interferon-inducible IFI16 and AIM2 innate immune sensors for cytosolic DNA in cellular senescence of human fibroblasts |
| 21471287 | The IFN-inducible IFI16 and AIM2 proteins act as innate immune sensors for cytosolic double-stranded DNA (dsDNA) |
| 21471287 | On sensing dsDNA, the IFI16 protein induces the expression of IFN-beta whereas the AIM2 protein forms an inflammasome, which promotes the secretion of IL-1beta |
| 21471287 | Given that the knockdown of IFI16 expression in human diploid fibroblasts (HDF) delays the onset of cellular senescence, we investigated the potential roles for the IFI16 and AIM2 proteins in cellular senescence |
| 21471287 | We found that increased IFI16 protein levels in old (vs |
| 21471287 | The knockdown of type I IFN-alpha receptor subunit, which reduced the basal levels of the IFI16 but not of the AIM2, protein delayed the onset of cellular senescence |
| 21471287 | Accordingly, increased constitutive levels of IFI16 and AIM2 proteins in ataxia telangiectasia mutated (ATM) HDFs were associated with the activation of the IFN signaling and increased levels of IL-1beta |
| 21471287 | The IFN-beta treatment of the young HDFs, which induced the expression of IFI16 and AIM2 proteins, activated a DNA damage response and also increased basal levels of IL-1beta |
| 21471287 | Interestingly, the knockdown of AIM2 expression in HDFs increased the basal levels of IFI16 protein and activated the IFN signaling |
| 21471287 | In contrast, the knockdown of the IFI16 expression in HDFs decreased the basal and dsDNA-induced activation of the IFN signaling |
| 21471287 | Collectively, our observations show differential roles for the IFI16 and AIM2 proteins in cellular senescence and associated secretory phenotype |
| 20052289 | Interferon-inducible IFI16, a negative regulator of cell growth, down-regulates expression of human telomerase reverse transcriptase (hTERT) gene |
| 20052289 | BACKGROUND: Increased levels of interferon (IFN)-inducible IFI16 protein (encoded by the IFI16 gene located at 1q22) in human normal prostate epithelial cells and diploid fibroblasts (HDFs) are associated with the onset of cellular senescence |
| 20052289 | Here, we report that increased levels of IFI16 protein in normal HDFs and in HeLa cells negatively regulate the expression of human telomerase reverse transcriptase (hTERT) gene |
| 20052289 | Using the optimized conditions, we report that treatment of HDFs with inhibitors of cell cycle progression, such as aphidicolin or CGK1026, which resulted in reduced steady-state levels of IFI16 mRNA and protein, was associated with increases in hTERT mRNA and protein levels and telomerase activity |
| 20052289 | In contrast, knockdown of IFI16 expression in cells increased the expression of c-Myc, a positive regulator of hTERT expression |
| 20052289 | Additionally, over-expression of IFI16 protein in cells inhibited the c-Myc-mediated stimulation of the activity of hTERT-luc-reporter and reduced the steady-state levels of c-Myc and hTERT |
| 20052289 | CONCLUSIONS/SIGNIFICANCE: These data demonstrated that increased levels of IFI16 protein in HDFs down-regulate the expression of hTERT gene |
| 20052289 | Our observations will serve basis to understand how increased cellular levels of the IFI16 protein may contribute to certain aging-dependent diseases |
| 19071156 | Knockdown of ATM kinase or IFI16 rescued IFN-gamma-induced cellular senescence |
| 18974396 | Expression of an IFN-inducible cellular senescence gene, IFI16, is up-regulated by p53 |
| 18974396 | IFN-inducible IFI16 protein (encoded by IFI16 gene at 1q23 |
| 18974396 | Increased expression of the IFI16 protein, a positive modulator of p53-mediated transcription, in normal old human diploid fibroblasts (HDF) is associated with cellular senescence-mediated cell growth arrest |
| 18974396 | However, the underlying mechanisms that contribute to transcriptional activation of the IFI16 gene in old HDFs remain to be elucidated |
| 18974396 | Here, we reported that functional activation of p53 in normal young HDFs and p53-null Saos2 cell line resulted in transcriptional activation of the IFI16 gene |
| 18974396 | We identified a potential p53 DNA-binding site (indicated as IFI16-p53-BS) in the 5'-regulatory region of the IFI16 gene |
| 18974396 | Furthermore, p53 associated with the 5'-regulatory region of the IFI16 gene in chromatin immunoprecipitation assays |
| 18974396 | Interestingly, p53 associated with the regulatory region of the IFI16 gene only on treatment of cells with DNA-damaging agents or in the old, but not in the young, HDFs |
| 18974396 | Importantly, our promoter-reporter assays, which were coupled with site-directed mutagenesis of IFI16-p53-BS, showed that p53 activates transcription of the IFI16 gene in HDFs through the p53 DNA-binding site |
| 18974396 | Together, our observations provide support for the idea that up-regulation of IFI16 expression by p53 and functional interactions between IFI16 protein and p53 contribute to cellular senescence |
| 17981573 | Interferon-inducible IFI16 protein in human cancers and autoimmune diseases |
| 17981573 | Interferon-inducible IFI16 protein (encoded by IFI16 gene located at 1q21 region) is a member of the p200-protein family |
| 17981573 | Consistent with this role of p200-family proteins, increased expression of IFI16 protein in normal human diploid fibroblasts and prostate epithelial cells is associated with cellular senescence-associated permanent cell growth arrest |
| 17981573 | Furthermore, reduced or loss of IFI16 expression in cells is associated with the development of certain cancers, such as breast and prostate cancer |
| 17981573 | Interestingly, recent studies have provided evidence that the constitutive and interferon-induced expression of the IFI16 gene varies among individuals and may depend on the race |
| 17981573 | These studies raise the possibility that alterations (increases or decreases) in the expression of IFI16 protein may contribute to the development of human diseases |
| 17981573 | In this review, we discuss how our understanding of the regulation of IFI16 expression and its role in cell growth regulation will help elucidate the molecular mechanisms that contribute to the development of various human diseases |
| 17569615 | IFI16 inhibits tumorigenicity and cell proliferation of bone and cartilage tumor cells |
| 17569615 | IFI16 is a member of the interferon-inducible p200-protein family, capable of modulating cell proliferation, and cellular senescence |
| 17569615 | In this study, these effects of IFI16 were studied in tumor cells derived from bone and cartilage |
| 17569615 | The level of IFI16 was markedly lower in human osteosarcomas as compared with its level in normal bone |
| 17569615 | Overexpression of functional IFI16 in human osteosarcoma and chondrosarcoma cell lines markedly inhibited colony formation, and significantly inhibited cell growth, an effect that could be reversed by introduction of gene specific siRNA into tumor cells |
| 17569615 | These inhibitory effects of IFI16 were associated with upregulation of p21 and inhibition of cyclin E, cyclin D1, c-Myc and Ras |
| 17569615 | In addition, ectopic expression of IFI16 in tumor cells increased senescence-associated beta-galactosidase and induced a senescence-like phenotype |
| 17569615 | In view of such effects, IFI16 might be a suitable target for therapeutic intervention in osteosarcoma and chondrosarcoma |
| 17339605 | IFI16 in human prostate cancer |
| 17339605 | Increased expression of IFI16 protein (encoded by the IFI16 gene) in normal human prostate epithelial cells is associated with cellular senescence-associated cell growth arrest |
| 17339605 | Consistent with a role for IFI16 protein in cellular senescence, the expression of IFI16 protein is either very low or not detectable in human prostate cancer cell lines |
| 17339605 | We now report that treatment of DU-145 and LNCaP prostate cancer cell lines with histone deacetylase inhibitor trichostatin A (TSA) or CGK1026 resulted in transcriptional activation of the IFI16 gene |
| 17339605 | The induction of IFI16 protein in LNCaP cells was dependent on the duration of TSA treatment |
| 17339605 | However, overexpression of exogenous Janus-activated kinase 1 protein in LNCaP cells and treatment of cells with IFNs (alpha and gamma) did not increase the expression of IFI16 |
| 17339605 | Instead, the transcriptional activation of IFI16 gene by TSA treatment of LNCaP cells was dependent on transcriptional activation by c-Jun/activator protein-1 transcription factor |
| 17339605 | Importantly, increased expression of IFI16 in LNCaP cells was associated with decreases in the expression of androgen receptor and apoptosis of cells |
| 17339605 | Conversely, knockdown of IFI16 expression in TSA-treated LNCaP cells increased androgen receptor protein levels with concomitant decreases in apoptosis |
| 17339605 | Together, our observations provide support for the idea that histone deacetylase-dependent transcriptional silencing of the IFI16 gene in prostate epithelial cells contributes to the development of prostate cancer |
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