title: The ubiquitin ligase TRIM56 regulates innate immune responses to intracellular double-stranded DNA.
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.
authors.affiliation: Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Tsuchida
authors.forename: Jian
authors.initials: J
authors.lastname: Zou
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Saitoh
authors.forename: Himanshu
authors.initials: H
authors.lastname: Kumar
authors.forename: Takayuki
authors.initials: T
authors.lastname: Abe
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Matsuura
authors.forename: Taro
authors.initials: T
authors.lastname: Kawai
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
mesh_terms: D004247:DNA / Q000276:immunology*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D016899:Interferon-beta / Q000276:immunology / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000276:immunology / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000276:immunology; D000099197:STING Protein
chemical_list: D004247:DNA; D016899:Interferon-beta; D008239:Lysine; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; C532857:STING1 protein, human; D000099197:STING Protein; C554560:TRIM56 protein, human; C403191:TBK1 protein, human