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

Author(s): Tetsuo Tsuchida, Jian Zou, Tatsuya Saitoh, Himanshu Kumar, Takayuki Abe, Yoshiharu Matsuura, Taro Kawai, Shizuo Akira

Publication date: 2010-11-24

Journal: Immunity

Keywords: DNA, immunology, HEK293 Cells, HeLa Cells, Humans, Immunity, Innate, Interferon-beta, metabolism, Lysine, Membrane Proteins, Promoter Regions, Genetic, Protein-Serine-Threonine Kinases, Ubiquitin-Protein Ligases, genetics, Ubiquitination

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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. Copyright © 2010 Elsevier Inc. All rights reserved.