The E3 ubiquitin ligase RNF5 targets virus-induced signaling adaptor for ubiquitination and degradation.
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.
Zhong
Bo
B
College of Life Sciences, Wuhan University, Wuhan, China.
Zhang
Yu
Y
Tan
Bo
B
Liu
Tian-Tian
TT
Wang
Yan-Yi
YY
Shu
Hong-Bing
HB
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
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C505371:MAVS protein, human; C111501:RNF5 protein, human; D044767:Ubiquitin-Protein Ligases