RNF26 Temporally Regulates Virus-Triggered Type I Interferon Induction by Two Distinct Mechanisms

Abstract

Viral infection triggers induction of type I interferons (IFNs), which are critical mediators of innate antiviral immune response. Mediator of IRF3 activation (MITA, also called STING) is an adapter essential for virus-triggered IFN induction pathways. How post-translational modifications regulate the activity of MITA is not fully elucidated. In expression screens, we identified RING finger protein 26 (RNF26), an E3 ubiquitin ligase, could mediate polyubiquitination of MITA. Interestingly, RNF26 promoted K11-linked polyubiquitination of MITA at lysine 150, a residue also targeted by RNF5 for K48-linked polyubiquitination. Further experiments indicated that RNF26 protected MITA from RNF5-mediated K48-linked polyubiquitination and degradation that was required for quick and efficient type I IFN and proinflammatory cytokine induction after viral infection. On the other hand, RNF26 was required to limit excessive type I IFN response but not proinflammatory cytokine induction by promoting autophagic degradation of IRF3. Consistently, knockdown of RNF26 inhibited the expression of IFNB1 gene in various cells at the early phase and promoted it at the late phase of viral infection, respectively. Furthermore, knockdown of RNF26 inhibited viral replication, indicating that RNF26 antagonizes cellular antiviral response. Our findings thus suggest that RNF26 temporally regulates innate antiviral response by two distinct mechanisms.

WDR82 Negatively Regulates Cellular Antiviral Response by Mediating TRAF3 Polyubiquitination in Multiple Cell Lines

“…TRAF3 is a key molecule in the cascade of RIG-I signaling pathway, and its K63-linked polyubiquitination is required for TBK1 recruitment and downstream events; additionally, the regulation of different forms of polyubiquitination chains emerged as critical to the regulation of innate immunity pathways (14,(27)(28)(29)(30)(31). To further elucidate the biochemical mechanisms, we investigate the impact of WDR82 in regulating TRAF3 polyubiquitination.…”

Matrix Metalloproteinase 9 Facilitates Hepatitis B Virus Replication through Binding with Type I Interferon (IFN) Receptor 1 To Repress IFN/JAK/STAT Signaling

“…A ubiquitination assay was performed as described previously (65). The cells were lysed in IP lysis buffer containing 1% SDS and heated for 5 min.…”

Quantitative Proteomics Reveals the Roles of Peroxisome-associated Proteins in Antiviral Innate Immune Responses*

“…This phenomenon is also the reason why we chose HepG2 as the host cell for our study focusing on viral-induced alterations in peroxisome-associated proteins. The SeV infection conditions, the MOI and the infection time were primarily based on our previous studies (30), to ensure that the proteomic data could be compared with those studies.…”

“…Western Blot-Proteins separation by SDS-PAGE (10% gel) and Western blotting were performed as previously described (30). The following antibodies were used in the experiments: mouse monoclonal anti-AIF (Santa Cruz, Dallas, TX, Cat.…”