The ubiquitin ligase TRIM56 regulates innate immune responses to intracellular double-stranded DNA

Immunity. 2010 Nov 24;33(5):765-76. doi: 10.1016/j.immuni.2010.10.013. Epub 2010 Nov 11.

Abstract

The innate immune system detects pathogen- and host-derived double-stranded DNA exposed to the cytosol and induces type I interferon (IFN) and other cytokines. Here, we identified interferon-inducible tripartite-motif (TRIM) 56 as a regulator of double-stranded DNA-mediated type I interferon induction. TRIM56 overexpression enhanced IFN-β promoter activation after double-stranded DNA stimulation whereas TRIM56 knockdown abrogated it. TRIM56 interacted with STING and targeted it for lysine 63-linked ubiquitination. This modification induced STING dimerization, which was a prerequisite for recruitment of the antiviral kinase TBK1 and subsequent induction of IFN-β. Taken together, these results indicate that TRIM56 is an interferon-inducible E3 ubiquitin ligase that modulates STING to confer double-stranded DNA-mediated innate immune responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / immunology*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Immunity, Innate*
  • Interferon-beta / immunology
  • Interferon-beta / metabolism
  • Lysine / metabolism
  • Membrane Proteins / metabolism
  • Promoter Regions, Genetic
  • Protein-Serine-Threonine Kinases / immunology
  • Protein-Serine-Threonine Kinases / metabolism
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination / immunology

Substances

  • Membrane Proteins
  • STING protein, human
  • Tripartite Motif Proteins
  • Interferon-beta
  • DNA
  • TRIM56 protein, human
  • Ubiquitin-Protein Ligases
  • Protein-Serine-Threonine Kinases
  • TBK1 protein, human
  • Lysine