ArticleNucleic acids research2023
IFI16 phase separation via multi-phosphorylation drives innate immune signaling.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 43 citations in OpenAlex.
- Cell death network regulation in HSV infection: immune evasion versus host defense.Apoptosis : an international journal on programmed cell death · 2026Review
- The Host Cell Factor Phosphatase-2A Subunit PR130 Restricts Replication of Herpes Simplex Virus Type-1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- IFI208, an interferon-stimulated gene, promotes host antiviral responses through liquid-liquid phase separation of MDA5.Nature communications · 2026Article
- Long-lived mammals contain more phosphorylation sites in the SIRT6 C-terminus that enhance PARP1 interaction and resistance to oxidative stress.GeroScience · 2026Article
- IFI16 restricts SARS-CoV-2 replication by disrupting nucleocapsid-driven phase separation.Communications biology · 2026Article
- The ISG Atlas: a loss-of-function analysis characterizes antiviral properties of interferon stimulated genes.Nature communications · 2026Article
- Phase separation of OPTN initiates mitophagy to orchestrate craniofacial bone mineralization.Autophagy · 2026Article
- Long-lived mammals contain more phosphorylation sites in the SIRT6 C-terminus that enhance PARP1 interaction and resistance to oxidative stress.bioRxiv : the preprint server for biology · 2026Article
- Review
- Article
- Deep learning model of post-translational modification regulating liquid-liquid phase separation.Communications chemistry · 2025Article
- Structural insights into the atypical filament assembly of pyrin domain-containing IFI16.The EMBO journal · 2025Article
- Missense mutations in intrinsically disordered protein regions link pathogenicity and phase separation.The Journal of biological chemistry · 2025Article
- Insights into Noncanonical and Diversified Functions of ABCF1: From Health to Disease.Journal of molecular biology · 2025Review
- Membraneless Organelles and Phase Separation in Tumours: Mechanisms and Prospects.Cell proliferation · 2025Review
- YY1 enhances HIF-1α stability in tumor-associated macrophages to suppress anti-tumor immunity of prostate cancer in mice.Nature communications · 2025Article
- Transient Poly(ADP-Ribose) Triggers FUS Condensation Hysteresis via a Prion-Like Mechanism.bioRxiv : the preprint server for biology · 2025Article
- Strategies and scheming: the war between PRRSV and host cells.Virology journal · 2025Review
- Innate immune mechanisms of infection: what we know and potential conserved mechanisms affecting sleep during infection.Neurobiology of sleep and circadian rhythms · 2025Article
- DNA-PK inhibition sustains the antitumor innate immune response in small cell lung cancer.iScience · 2025Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The interferon inducible protein 16 (IFI16) is a prominent sensor of nuclear pathogenic DNA, initiating innate immune signaling and suppressing viral transcription. However, little is known about mechanisms that initiate IFI16 antiviral functions or its regulation within the host DNA-filled nucleus. Here, we provide in vitro and in vivo evidence to establish that IFI16 undergoes liquid-liquid phase separation (LLPS) nucleated by DNA. IFI16 binding to viral DNA initiates LLPS and induction of cytokines during herpes simplex virus type 1 (HSV-1) infection. Multiple phosphorylation sites within an intrinsically disordered region (IDR) function combinatorially to activate IFI16 LLPS, facilitating filamentation. Regulated by CDK2 and GSK3β, IDR phosphorylation provides a toggle between active and inactive IFI16 and the decoupling of IFI16-mediated cytokine expression from repression of viral transcription. These findings show how IFI16 switch-like phase transitions are achieved with temporal resolution for immune signaling and, more broadly, the multi-layered regulation of nuclear DNA sensors.
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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.