TRIM9 short isoform preferentially promotes DNA and RNA virus-induced production of type I interferon by recruiting GSK3β to TBK1.

ABSTRACT: Type I interferon (IFN) is an important component of antiviral innate immune signaling mediated by viral DNA and RNA recognition by the DNA sensor cGAS and RNA sensors RIG-I and MDA5. Activation of these DNA and RNA sensors leads to the recruitment of STING and MAVS, respectively, and converges on TANK-binding kinase 1 (TBK1) signaling for subsequent phosphorylation of IFN regulatory factor 3 (IRF3). However, the mechanisms that control TBK1 activation are still poorly defined. Here, we identify tripartite motif 9 short isoform (TRIM9s) as a positive regulator in type I IFN signaling. Upon viral infection, TRIM9s undergoes Lys-63-linked auto-polyubiquitination and serves as a platform to bridge GSK3β to TBK1, leading to the activation of IRF3 signaling. Interestingly, we found that TRIM9s

SUBMITTER: Qin Y 

PROVIDER: S-EPMC4856760 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature