TRIM56 is an essential component of the TLR3 antiviral signaling pathway

Yang Shen, Nan L. Li, Jie Wang, Baoming Liu, Sandra Lester, Kui Li

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Members of the tripartite motif (TRIM) proteins are being recognized as important regulators of host innate immunity. However, specific TRIMs that contribute to TLR3-mediated antiviral defense have not been identified. We show here that TRIM56 is a positive regulator of TLR3 signaling. Overexpression of TRIM56 substantially potentiated extracellular dsRNA-induced expression of interferon (IFN)-β and interferon-stimulated genes (ISGs), while knockdown of TRIM56 greatly impaired activation of IRF3, induction of IFN-β and ISGs, and establishment of an antiviral state by TLR3 ligand and severely compromised TLR3-mediated chemokine induction following infection by hepatitis C virus. The ability to promote TLR3 signaling was independent of the E3 ubiquitin ligase activity of TRIM56. Rather, it correlated with a physical interaction between TRIM56 and TRIF. Deletion of the C-terminal portion of TRIM56 abrogated the TRIM56-TRIF interaction as well as the augmentation of TLR3-mediated IFN response. Together, our data demonstrate TRIM56 is an essential component of the TLR3 antiviral signaling pathway and reveal a novel role for TRIM56 in innate antiviral immunity.

Original languageEnglish (US)
Pages (from-to)36404-36413
Number of pages10
JournalJournal of Biological Chemistry
Volume287
Issue number43
DOIs
StatePublished - Oct 19 2012

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Interferons
Antiviral Agents
Innate Immunity
Genes
Gene Knockdown Techniques
Ubiquitin-Protein Ligases
Viruses
Chemokines
Hepacivirus
Chemical activation
Ligands
Infection
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

TRIM56 is an essential component of the TLR3 antiviral signaling pathway. / Shen, Yang; Li, Nan L.; Wang, Jie; Liu, Baoming; Lester, Sandra; Li, Kui.

In: Journal of Biological Chemistry, Vol. 287, No. 43, 19.10.2012, p. 36404-36413.

Research output: Contribution to journalArticle

Shen, Yang ; Li, Nan L. ; Wang, Jie ; Liu, Baoming ; Lester, Sandra ; Li, Kui. / TRIM56 is an essential component of the TLR3 antiviral signaling pathway. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 43. pp. 36404-36413.
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