Autoubiquitination of TRIM26 links TBK1 to NEMO in RLR-mediated innate antiviral immune response

J Mol Cell Biol. 2016 Feb;8(1):31-43. doi: 10.1093/jmcb/mjv068. Epub 2015 Nov 26.


The transcription factors IRF3 and NF-κB are required for the expression of many genes involved in antiviral innate immune response, including type I interferons (IFNs) and proinflammatory cytokines. It is well established that TBK1 is an essential kinase engaged downstream of multiple pattern-recognition receptors (PRRs) to mediate IRF3 phosphorylation and activation, whereas the precise mechanisms of TBK1 activation have not been fully elucidated yet. Here, we identified tripartite motif 26 (TRIM26) as an important regulator for RNA virus-triggered innate immune response. Knockdown of TRIM26 impaired virus-triggered IRF3, NF-κB activation, IFN-β induction, and cellular antiviral response. TRIM26 was physically associated with TBK1 independent of viral infection. As an E3 ligase, TRIM26 underwent autoubiquitination upon viral infection. Ubiquitinated TRIM26 subsequently associated with NEMO, thus bridging TBK1-NEMO interaction, which is critical for the recruitment of TBK1 to the VISA signalsome and activation of TBK1. Our findings suggest that TRIM26 is an important regulator of innate immune responses against RNA viruses, which functions by bridging TBK1 to NEMO and mediating the activation of TBK1.

Keywords: NEMO; TBK1; TRIM26; antiviral response; ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA-Binding Proteins / metabolism*
  • HEK293 Cells
  • Humans
  • I-kappa B Kinase / metabolism*
  • Immunity, Innate / physiology
  • Protein Binding
  • Protein-Serine-Threonine Kinases / metabolism*
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases
  • Ubiquitination / physiology


  • DNA-Binding Proteins
  • IKBKG protein, human
  • Tripartite Motif Proteins
  • TRIM26 protein, human
  • Ubiquitin-Protein Ligases
  • Protein-Serine-Threonine Kinases
  • TBK1 protein, human
  • I-kappa B Kinase