title: The E3 ubiquitin ligase TRIM21 negatively regulates the innate immune response to intracellular double-stranded DNA.
abstract: DDX41 is a sensor of intracellular double-stranded DNA (dsDNA) in myeloid dendritic cells (mDCs) that triggers a type I interferon response via the signaling adaptor STING. We identified the E3 ligase TRIM21 as a DDX41-interacting protein and found that knockdown of or deficiency in TRIM21 resulted in enhanced type I interferon responses to intracellular dsDNA and DNA viruses. Overexpression of TRIM21 resulted in more degradation of DDX41 and less production of interferon-β (IFN-β) in response to intracellular dsDNA. The SPRY-PRY domain of TRIM21 interacted with the DEADc domain of DDX41. Lys9 and Lys115 of DDX41 were the targets of TRIM21-mediated ubiquitination. TRIM21 is therefore an interferon-inducible E3 ligase that induces the Lys48 (K48)-linked ubiquitination and degradation of DDX41 and negatively regulates the innate immune response to intracellular dsDNA.
authors.affiliation: Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, Texas, USA.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Musheng
authors.initials: M
authors.lastname: Bao
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.forename: Leiyun
authors.initials: L
authors.lastname: Weng
authors.forename: Bin
authors.initials: B
authors.lastname: Yuan
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics / Q000276:immunology*; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology; D008239:Lysine / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D030102:Orthoreovirus, Mammalian / Q000502:physiology; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D012261:Ribonucleoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D054875:Ubiquitination; D018116:Vesiculovirus / Q000502:physiology; D000099207:SS-A Antigen; D000099197:STING Protein
chemical_list: D004247:DNA; D004279:DNA, Viral; D016899:Interferon-beta; D008239:Lysine; D008565:Membrane Proteins; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C530855:Sting1 protein, mouse; D000099197:STING Protein