title: TRIM4 modulates type I interferon induction and cellular antiviral response by targeting RIG-I for K63-linked ubiquitination.
abstract: RIG-I is a pivotal cytoplasmic sensor that recognizes different species of viral RNAs. This recognition leads to activation of the transcription factors NF-κB and IRF3, which collaborate to induce type I interferons (IFNs) and innate antiviral response. In this study, we identified the TRIM family protein TRIM4 as a positive regulator of RIG-I-mediated IFN induction. Overexpression of TRIM4 potentiated virus-triggered activation of IRF3 and NF-κB, as well as IFN-β induction, whereas knockdown of TRIM4 had opposite effects. Mechanistically, TRIM4 associates with RIG-I and targets it for K63-linked polyubiquitination. Our findings demonstrate that TRIM4 is an important regulator of the virus-induced IFN induction pathways by mediating RIG-I for K63-linked ubiquitination.
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Ai-Ping
authors.initials: AP
authors.lastname: Mao
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Hu
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Shu
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D008239:Lysine / Q000378:metabolism*; D025821:Polyubiquitin / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011971:Receptors, Immunologic; D029082:Sendai virus / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination / Q000187:drug effects*
chemical_list: D002352:Carrier Proteins; D011971:Receptors, Immunologic; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D025821:Polyubiquitin; D016899:Interferon-beta; C084523:TRIM25 protein, human; D044767:Ubiquitin-Protein Ligases; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D008239:Lysine
keywords: RIG-I; TRIM4; antiviral response; type I interferon; ubiquitination