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The Ubiquitin Ligase TRIM56 Regulates Innate Immune Responses to Intracellular Double-Stranded DNA. (Associate Prof. Kawai & Prof. Akira in Immunity)

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.


20101206_Kawai_Fig_ENG.jpg
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Contact:

Taro Kawai
tkawai@biken.osaka-u.ac.jp

Shizuo Akira
sakira@biken.osaka-u.ac.jp
Laboratory of Host Diffense
Immunology Frontier Research Center (IFReC), Osaka University

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