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RESEARCH PRODUCT

The Mitochondrial Targeting Chaperone 14-3-3ε Regulates a RIG-I Translocon that Mediates Membrane Association and Innate Antiviral Immunity

Michael G. KatzeMichael GaleYueh Ming LooStacy M. HornerHelene Minyi LiuGregory A. Zornetzer

subject

TRIM25Cancer ResearchUbiquitin-Protein Ligasesviruseschemical and pharmacologic phenomenaHepacivirusMicrobiologyAntiviral AgentsModels BiologicalArticleCell LineDEAD-box RNA HelicasesTripartite Motif Proteins03 medical and health sciences0302 clinical medicineVirologyImmunology and Microbiology(all)Protein Interaction MappingHumansReceptors ImmunologicDEAD Box Protein 58Molecular Biology030304 developmental biology0303 health sciencesInnate immune systembiologyRIG-IRNAMembrane Proteinsvirus diseasesRNA virusbiochemical phenomena metabolism and nutritionbiology.organism_classificationTranslocon3. Good healthCell biology14-3-3 Proteins030220 oncology & carcinogenesisChaperone (protein)biology.proteinDEAD Box Protein 58Parasitologybiological phenomena cell phenomena and immunityMolecular ChaperonesProtein BindingTranscription Factors

description

SummaryRIG-I is a cytosolic pathogen recognition receptor that initiates immune responses against RNA viruses. Upon viral RNA recognition, antiviral signaling requires RIG-I redistribution from the cytosol to membranes where it binds the adaptor protein, MAVS. Here we identify the mitochondrial targeting chaperone protein, 14-3-3ε, as a RIG-I-binding partner and essential component of a translocation complex or “translocon” containing RIG-I, 14-3-3ε, and the TRIM25 ubiquitin ligase. The RIG-I translocon directs RIG-I redistribution from the cytosol to membranes where it mediates MAVS-dependent innate immune signaling during acute RNA virus infection. 14-3-3ε is essential for the stable interaction of RIG-I with TRIM25, which facilitates RIG-I ubiquitination and initiation of innate immunity against hepatitis C virus and other pathogenic RNA viruses. Our results define 14-3-3ε as a key component of a RIG-I translocon required for innate antiviral immunity.

yearjournalcountryeditionlanguage
2012-05-01Cell Host & Microbe
10.1016/j.chom.2012.04.006http://dx.doi.org/10.1016/j.chom.2012.04.006