The Ubiquitin Ligase TRIM56 Regulates Innate Immune Responses to Intracellular Double-Stranded DNA

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 inducti...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2010-11, Vol.33 (5), p.765-776
Main Authors: Tsuchida, Tetsuo, Zou, Jian, Saitoh, Tatsuya, Kumar, Himanshu, Abe, Takayuki, Matsuura, Yoshiharu, Kawai, Taro, Akira, Shizuo
Format: Article
Language:English
Subjects:
Cloning
Cytosol
Deoxyribonucleic acid
DNA
DNA - immunology
Gene expression
HEK293 Cells
HeLa Cells
Humans
Immune system
Immunity, Innate
Interferon-beta - immunology
Interferon-beta - metabolism
Kinases
Lysine - metabolism
Membrane Proteins - metabolism
Plasmids
Promoter Regions, Genetic
Protein-Serine-Threonine Kinases - immunology
Protein-Serine-Threonine Kinases - metabolism
RNA polymerase
Rodents
Signal transduction
Tripartite Motif Proteins
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
Ubiquitination - immunology
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Summary: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. ► TRIM56 expression is induced by dsDNA and poly (I:C) stimulation ► TRIM56 enhanced IFN-β promoter activation after dsDNA stimulation ► TRIM56 promoted K63-linked ubiquitination and dimerization of STING ► These modifications are required to form a complex with TBK1 and induce IFN-β
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2010.10.013