ArticleProceedings of the National Academy of Sciences of the United States of America2012
Acetylation modulates cellular distribution and DNA sensing ability of interferon-inducible protein IFI16.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 205 papers.
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Who cites it
205 citing papers in PubMed, 293 citations in OpenAlex.
- Expulsion of nuclear DNA to the cytoplasm after viral entry: A mechanism for activation of the cGAS pathway.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- IFI16 restricts SARS-CoV-2 replication by disrupting nucleocapsid-driven phase separation.Communications biology · 2026Article
- IFI204 drives gasdermin D-mediated mitochondrial permeabilization to amplify neuronal pyroptosis in ischemic stroke.Journal of neuroinflammation · 2026Article
- Proximity proteomics reveals a role for IFI16 during human coronavirus infection.bioRxiv : the preprint server for biology · 2026Article
- Review
- Structural insights into the atypical filament assembly of pyrin domain-containing IFI16.The EMBO journal · 2025Article
- IFI204 RestrictsMicroorganisms · 2025Article
- Innate immune sensing and signaling: Co-opted for genome surveillance? Implications for tumorigenesis.DNA repair · 2025Review
- Lactylation and viral infections: A novel link between metabolic reprogramming and immune regulation.PLoS pathogens · 2025Review
- Direct relationship between protein expression and progeny yield of herpes simplex virus 1.mBio · 2025Article
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- IFI16 recruits HDAC1 and HDAC2 to deacetylate the Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA), facilitating latency.Journal of virology · 2025Article
- Infection-induced lysine lactylation enables herpesvirus immune evasion.Science advances · 2025Article
- EMCV VP2 degrades IFI16 through Caspase-dependent apoptosis to evade IFI16-STING pathway.Virology journal · 2024Article
- Controlling Much? Viral Control of Host Chromatin Dynamics.Annual review of virology · 2024Review
- Interferon-γ inducible factor 16 (IFI16) restricts adeno-associated virus type 2 (AAV2) transduction in an immune-modulatory independent way.Journal of virology · 2024Article
- Liquid-liquid phase separation in innate immunity.Trends in immunology · 2024Review
- When DNA-damage responses meet innate and adaptive immunity.Cellular and molecular life sciences : CMLS · 2024Review
- Article
145 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Detection of pathogenic nucleic acids is essential for mammalian innate immunity. IFN-inducible protein IFI16 has emerged as a critical sensor for detecting pathogenic DNA, stimulating both type I IFN and proinflammatory responses. Despite being predominantly nuclear, IFI16 can unexpectedly sense pathogenic DNA in both the cytoplasm and the nucleus. However, the mechanisms regulating its localization and sensing ability remain uncharacterized. Here, we propose a two-signal model for IFI16 sensing. We first identify an evolutionarily conserved multipartite nuclear localization signal (NLS). Next, using FISH and immunopurification, we demonstrate that IFI16 detects HSV-1 DNA primarily in the nucleus, requiring a functional NLS. Furthermore, we establish a localization-dependent IFN-β induction mediated by IFI16 in response to HSV-1 infection or viral DNA transfection. To identify mechanisms regulating the secondary cytoplasmic localization, we explored IFI16 posttranslation modifications. Combinatorial MS analyses identified numerous acetylations and phosphorylations on endogenous IFI16 in lymphocytes, in which we demonstrate an IFI16-mediated IFN-β response. Importantly, the IFI16 NLS was acetylated in lymphocytes, as well as in macrophages. Mutagenesis and nuclear import assays showed that NLS acetylations promote cytoplasmic localization by inhibiting nuclear import. Additionally, broad-spectrum deacetylase inhibition triggered accumulation of cytoplasmic IFI16, and we identify the acetyltransferase p300 as a regulator of IFI16 localization. Collectively, these studies establish acetylation as a molecular toggle of IFI16 distribution, providing a simple and elegant mechanism by which this versatile sensor detects pathogenic DNA in a localization-dependent manner.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.