ArticleNature immunology2025
STING signals to NF-κB from late endolysosomal compartments using IRF3 as an adaptor.
Article in Nature immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- PARP7 inhibition and a STING agonist potentiate radiation-induced immunogenicity in glioblastoma.Oncoimmunology · 2026Article
- From mitochondria to innate immunity: The mtDNA-driven cGAS/STING-NLRP3 cascade and its therapeutic implications in neurodegenerative diseases (Review).Experimental and therapeutic medicine · 2026Review
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- The cGAS-STING pathway: mechanistic basis, dual biological functions and translational therapeutic advances.Apoptosis : an international journal on programmed cell death · 2026Review
- STING agonist profiling by nucleotide library defines structural determinants of cyclic dinucleotide recognition.iScience · 2026Article
- PARP7 inhibitors enhance the immunogenic effects of radiation in pancreatic cancer cells.Molecular therapy. Oncology · 2026Article
- Atlas-ing STING mutations to advance fundamental understanding and clinical translation.Cell research · 2026Article
- TRIM28 SUMOylates IRF3 in astrocytes to drive neutrophils infiltration and ischemic cerebral injury.Cell death and differentiation · 2026Article
- Silica Nanoparticles Elicit Pulmonary Inflammation via STING-Dependent Activation of NF-κB p65 Signaling Pathway.Biomolecules · 2026Article
- The mutational landscape of STING-induced immunity.Nature · 2026Article
- The Role and Therapeutic Potential of the STING Signaling Pathway in the Pathogenesis of Diabetic Nephropathy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Expanding roles of cGAS-STING signaling in neuroinflammation.The Journal of clinical investigation · 2026Review
- Noncanonical IRF3 function mediates STING-dependent pro-inflammatory cytokine production in macrophages.EMBO reports · 2026Article
- ERAD inhibitor Eeyarestatin I (EerI) suppresses duck plague virus by restoring STING-mediated antiviral immunity.Poultry science · 2026Article
- ESCRT-Mimetic Nanodegrader Targets STING for Anti-Inflammatory Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A PI(3,5)PNature communications · 2026Article
- Structural Evolution and Immunomodulatory Versatility of Fungal Immunomodulatory Proteins: Insights into Mechanisms and Bioproduction Strategies.Journal of agricultural and food chemistry · 2026Review
- Unlocking the black box: multimodal imaging and quantitative analysis of plant vesicular trafficking.Advanced biotechnology · 2026Review
- Marine Bromophenol Derivatives as a Novel Class of Potent Small-Molecule STING Agonists.Current issues in molecular biology · 2026Article
- STING signaling pathway: An oasis in the glioblastoma immune desert.Theranostics · 2026Review
Corrections and comments
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Authors and funding
40 authors.
Funding
Abstract
NF-κB is central for activation of immune responses. Cytosolic DNA activates the cGAS-STING pathway to induce type I interferons (IFNs) and signaling through NF-κB, thus instigating host defenses and pathological inflammation. However, the mechanism underlying STING-induced NF-κB activation is unknown. Here we report that STING activates NF-κB in a delayed manner, following exit from the Golgi to endolysosomal compartments. Activation of NF-κB is dependent on the IFN-inducing transcription factor IRF3 but is independent of type I IFN signaling. This activation pattern is evolutionarily conserved in tetrapods. Mechanistically, the monomer IRF3 is recruited to STING pS358, with delayed kinetics relative to IRF3 recruitment to STING pS366, which promotes type I IFN responses. IRF3 engagement with STING pS358 induces trafficking to late endolysosomal compartments, supporting recruitment of TRAF6 and activation of NF-κB. We identify a TRAF6 binding motif in IRF3 that facilitates recruitment of TRAF6. This work defines a signaling surface on STING and a function for IRF3 as an adaptor in immune signaling. These findings indicate that STING signaling to NF-κB is enabled only within a short time window between exit from the Golgi and lysosomal degradation, possibly limiting inflammation under homeostatic and danger-sensing conditions.
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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.