ArticleNature structural & molecular biology2023
MAVS deSUMOylation by SENP1 inhibits its aggregation and antagonizes IRF3 activation.
Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- ALOX15 orchestrates mitochondrial antiviral immunity and serves as a host target for anti-influenza therapy.Nature immunology · 2026Article
- IFI208, an interferon-stimulated gene, promotes host antiviral responses through liquid-liquid phase separation of MDA5.Nature communications · 2026Article
- Review
- Reprogramming gut microenvironment for the treatment of acute severe ulcerative colitis via a synergistic therapy of necroptosis blockade and organoid transplantation.Nature communications · 2026Article
- CSDE1 promotes viral immune evasion through RNA-dependent and phosphorylation-modulated liquid-liquid phase separation.Nature communications · 2026Article
- Metabolic-Epigenetic Crosstalk in Takayasu Arteritis: The ANK2-MAVS-IL-8 Axis as a Novel Therapeutic Paradigm.International journal of molecular sciences · 2026Review
- Machine Learning-Guided Engineering of Protein Phase Separation Properties in Immune Regulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- SENP5 enhances antiviral innate immunity by promoting AURKA-dependent STAT2 phosphorylation.Cell communication and signaling : CCS · 2026Article
- Nervous necrosis virus capsid protein functions as a SUMO E3 ligase to activate MAVS-dependent NF-κB signaling.Cellular and molecular life sciences : CMLS · 2026Article
- Post-translational control of MAVS signaling: linking mitochondrial antiviral immunity to metabolic and cellular stress contexts.Frontiers in physiology · 2026Review
- Old dogs-new tricks: multifaceted functions of MAVS beyond antivirus activity in human health and diseases.Cell & bioscience · 2025Review
- METTL10-Mediated PIAS3 Methylation Links Purine Metabolism to Gastric Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Aging impairs the antiviral defense in Caenorhabditis elegans due to loss of DRH-1/RIG-I deSUMOylation by ULP-4/SENP7.EMBO reports · 2025Article
- The RIG-I-like receptor family of immune proteins.Molecular cell · 2025Review
- SENP1: A perspective from immune cells to disease (Review).Oncology reports · 2025Review
- SENP5 drives breast cancer progression through deSUMOYlation of CDK1.Breast cancer research : BCR · 2025Article
- The SUMO Pathway.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Pathogen-induced hijacking of host SUMOylation: from molecular mechanisms and prospects for therapeutic modulation.Frontiers in immunology · 2025Review
- Palmitoylation acts as a checkpoint for MAVS aggregation to promote antiviral innate immune responses.The Journal of clinical investigation · 2024Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial antiviral signaling protein (MAVS) is an adapter that recruits and activates IRF3. However, the mechanisms underpinning the interplay between MAVS and IRF3 are largely unknown. Here we show that small ubiquitin-like modifier (SUMO)-specific protease 1 negatively regulates antiviral immunity by deSUMOylating MAVS. Upon virus infection, PIAS3-induced poly-SUMOylation promotes lysine 63-linked poly-ubiquitination and aggregation of MAVS. Notably, we observe that SUMO conjugation is required for MAVS to efficiently produce phase-separated droplets through association with a newly identified SUMO-interacting motif (SIM) in MAVS. We further identify a yet-unknown SIM in IRF3 that mediates its enrichment to the multivalent MAVS droplets. Conversely, IRF3 phosphorylation at crucial residues close to SIM rapidly disables SUMO-SIM interactions and releases activated IRF3 from MAVS. Our findings implicate SUMOylation in MAVS phase separation and suggest a thus far unknown regulatory process by which IRF3 can be efficiently recruited and released to facilitate timely activation of antiviral responses.
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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.