title: TRIM14 is a mitochondrial adaptor that facilitates retinoic acid-inducible gene-I-like receptor-mediated innate immune response.
abstract: Innate immunity provides the first line of host defense against invading microbial pathogens. This defense involves retinoic acid-inducible gene-I-like receptors that detect viral RNA and activate the mitochondrial antiviral-signaling (MAVS) protein, an adaptor protein, leading to activation of the innate antiviral immune response. The mechanisms by which the MAVS signalosome assembles on mitochondria are only partially understood. Here, we identify tripartite motif 14 (TRIM14) as a mediator in the immune response against viral infection. TRIM14 localizes to the outer membrane of mitochondria and interacts with MAVS. Upon viral infection, TRIM14 undergoes Lys-63-linked polyubiquitination at Lys-365 and recruits NF-κB essential modulator to the MAVS signalosome, leading to the activation of both the IFN regulatory factor 3 and NF-κB pathways. Knockdown of TRIM14 disrupts the association between NF-κB essential modulator and MAVS and attenuates the antiviral response. Our results indicate that TRIM14 is a component of the mitochondrial antiviral immunity that facilitates the immune response mediated by retinoic acid-inducible gene-I-like receptors.
authors.affiliation: Chinese National Health and Family Planning Commission Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xue
authors.initials: X
authors.lastname: Jia
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Xue
authors.forename: Zhixun
authors.initials: Z
authors.lastname: Dou
authors.forename: Yijie
authors.initials: Y
authors.lastname: Ma
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Zhao
authors.forename: Zhengfan
authors.initials: Z
authors.lastname: Jiang
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.forename: Qi
authors.initials: Q
authors.lastname: Jin
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002850:Chromatography, Gel; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007113:Immunity, Innate / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D008856:Microscopy, Fluorescence; D046912:Multiprotein Complexes / Q000378:metabolism*; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D014212:Tretinoin / Q000378:metabolism*; D000070584:Tripartite Motif Proteins; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D017931:DNA Primers; C491731:IKBKG protein, human; D047908:Intracellular Signaling Peptides and Proteins; C505371:MAVS protein, human; D046912:Multiprotein Complexes; C481145:TRIM14 protein, human; D000070584:Tripartite Motif Proteins; D014212:Tretinoin; D051550:I-kappa B Kinase