ArticleMolecular cancer research : MCR2011
Differential roles for the interferon-inducible IFI16 and AIM2 innate immune sensors for cytosolic DNA in cellular senescence of human fibroblasts.
Article in Molecular cancer research : MCR, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47 citing papers in PubMed, 91 citations in OpenAlex.
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- Artemis (DCLRE1C) Acts as a Target to Enhance Radiotherapy Response in Triple-Negative Breast Cancer.Cancers · 2025Article
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- Exploring circulating cell-free DNA as a biomarker and as an inducer of AIM2-inflammasome-mediated inflammation in patients with abdominal aortic aneurysm.Scientific reports · 2025Article
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- The role of IFI16 in regulating PANoptosis and implication in heart diseases.Cell death discovery · 2024Review
- Regulation of cellular senescence by innate immunity.Biophysics reports · 2023Article
- Potential Therapeutic Value of the STING Inhibitors.Molecules (Basel, Switzerland) · 2023Review
- Niclosamide as a chemical probe for analyzing SARS-CoV-2 modulation of host cell lipid metabolism.Frontiers in microbiology · 2023Article
- Nuclear antiviral innate responses at the intersection of DNA sensing and DNA repair.Trends in microbiology · 2022Review
- A study on DNA methylation modifying natural compounds identified EGCG for induction of IFI16 gene expression related to the innate immune response in cancer cells.Oncology letters · 2022Article
- Merkel Cell Polyomavirus Infection Induces an Antiviral Innate Immune Response in Human Dermal Fibroblasts.Journal of virology · 2021Article
- Human Prostate Epithelial Cells Activate the AIM2 Inflammasome upon Cellular Senescence: Role of POP3 Protein in Aging-Related Prostatic Inflammation.Life (Basel, Switzerland) · 2021Article
- Type I Interferon Increases Inflammasomes Associated Pyroptosis in the Salivary Glands of Patients with Primary Sjögren's Syndrome.Immune network · 2020Article
- Role of inflammasomes in the pathogenesis of periodontal disease and therapeutics.Periodontology 2000 · 2020Review
- One Step Ahead: Herpesviruses Light the Way to Understanding Interferon-Stimulated Genes (ISGs).Frontiers in microbiology · 2020Review
- Intracellular sensing of viral genomes and viral evasion.Experimental & molecular medicine · 2019Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The IFN-inducible IFI16 and AIM2 proteins act as innate immune sensors for cytosolic double-stranded DNA (dsDNA). On sensing dsDNA, the IFI16 protein induces the expression of IFN-β whereas the AIM2 protein forms an inflammasome, which promotes the secretion of IL-1β. 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. We found that increased IFI16 protein levels in old (vs. young) HDFs were associated with the induction of IFN-β. In contrast, increased levels of the AIM2 protein in the senescent (vs. old) HDFs were associated with increased production of IL-1β. The knockdown of type I IFN-α receptor subunit, which reduced the basal levels of the IFI16 but not of the AIM2, protein delayed the onset of cellular senescence. 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-1β. The IFN-β 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-1β. Interestingly, the knockdown of AIM2 expression in HDFs increased the basal levels of IFI16 protein and activated the IFN signaling. In contrast, the knockdown of the IFI16 expression in HDFs decreased the basal and dsDNA-induced activation of the IFN signaling. Collectively, our observations show differential roles for the IFI16 and AIM2 proteins in cellular senescence and associated secretory phenotype.
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