title: RING finger protein 11 targets TBK1/IKKi kinases to inhibit antiviral signaling.
abstract: A key feature of the innate antiviral immune response is a rapid nonspecific response to virus infection largely mediated by the induction and extracellular secretion of type I interferons (IFNs) that restrict virus replication. Cytoplasmic sensors such as RIG-I recognize viral RNA and trigger antiviral signaling pathways that upregulate IFN transcription. However, it remains largely unknown how antiviral signaling is negatively regulated to maintain homeostasis after the elimination of virus. In this report, we have identified the RING domain-containing protein RING finger 11 (RNF11) as a novel negative regulator of innate antiviral signaling. Overexpression of RNF11 downregulated IFN-β expression and enhanced viral replication whereas siRNA-mediated knockdown of RNF11 suppressed viral replication. RNF11 interacted with the noncanonical IKK kinases TBK1/IKKi and attenuated their Lys63-linked polyubiquitination by blocking interactions with the E3 ligase TRAF3. The inhibitory function of RNF11 was dependent on the ubiquitin-binding adaptor molecule TAX1BP1 which was required for RNF11 to target TBK1/IKKi. Collectively, these results indicate that RNF11 functions together with TAX1BP1 to restrict antiviral signaling and IFN-β production.
authors: Department of Microbiology and Immunology, The University of Miami, Miller School of Medicine, Miami, Florida, United States of America.
authors: Soratree
authors: S
authors: Charoenthongtrakul
authors: Linlin
authors: L
authors: Gao
authors: Kislay
authors: K
authors: Parvatiyar
authors: David
authors: D
authors: Lee
authors: Edward W
authors: EW
authors: Harhaj
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000276:immunology* / Q000821:virology; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D048008:TNF Receptor-Associated Factor 3 / Q000235:genetics / Q000276:immunology; D054875:Ubiquitination; D018116:Vesiculovirus / Q000276:immunology; D014779:Virus Replication
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; C404508:RNF11 protein, human; C120635:TAX1BP1 protein, human; D048008:TNF Receptor-Associated Factor 3; D016899:Interferon-beta; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human