@article {Zhong6249, author = {Zhong, Bo and Zhang, Yu and Tan, Bo and Liu, Tian-Tian and Wang, Yan-Yi and Shu, Hong-Bing}, title = {The E3 Ubiquitin Ligase RNF5 Targets Virus-Induced Signaling Adaptor for Ubiquitination and Degradation}, volume = {184}, number = {11}, pages = {6249--6255}, year = {2010}, doi = {10.4049/jimmunol.0903748}, publisher = {American Association of Immunologists}, abstract = {Viral infection activates transcription factors, such as NF-κB 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.}, issn = {0022-1767}, URL = {https://www.jimmunol.org/content/184/11/6249}, eprint = {https://www.jimmunol.org/content/184/11/6249.full.pdf}, journal = {The Journal of Immunology} }