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


MeSH Major

  • Adipocytes
  • Genes, MHC Class II
  • Inflammation
  • Obesity


  • 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 selectively inhibits the production of pro-inflammatory cytokines, but enhances the expression of type I IFNs as well as IFN-stimulated genes, in response to viral infection. Our findings reveal novel dual functions of TRIM9s in antiviral immunity, which serve to balance pro-inflammatory response and production of type I IFNs.

publication date

  • May 2016



  • Academic Article



  • eng

PubMed Central ID

  • PMC4856760

Digital Object Identifier (DOI)

  • 10.1038/cr.2016.27

PubMed ID

  • 26915459

Additional Document Info

start page

  • 613

end page

  • 28


  • 26


  • 5