title: The E3 ubiquitin ligase RNF5 targets virus-induced signaling adaptor for ubiquitination and degradation.
abstract: Viral infection activates transcription factors, such as NF-kappaB and IFN regulatory factor 3, which collaborate to induce type I IFNs and elicit innate antiviral response. Virus-induced signaling adaptor (VISA) has been identified as a critical adaptor required for virus-triggered induction of type I IFNs. In this study, we showed that the E3 ubiquitin ligase RING-finger protein 5 (RNF5) interacted with VISA at mitochondria in a viral infection-dependent manner. Domain mapping experiments indicated that the C-terminal transmembrane domain of VISA was required for its interaction with RNF5. RNF5 targeted VISA at K362 and K461 for K48-linked ubiquitination and degradation after viral infection, whereas knockdown of RNF5 reversed virus-induced downregulation of VISA at the early phase. These findings suggest that RNF5-mediated ubiquitination and degradation of VISA is one of the mechanisms of the regulation of virus-triggered induction of type I IFNs and cellular antiviral response.
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhong
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Tan
authors.forename: Tian-Tian
authors.initials: TT
authors.lastname: Liu
authors.forename: Yan-Yi
authors.initials: YY
authors.lastname: Wang
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Shu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D016297:Mutagenesis, Site-Directed; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination; D014777:Virus Diseases / Q000276:immunology* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C505371:MAVS protein, human; C111501:RNF5 protein, human; D044767:Ubiquitin-Protein Ligases