{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lin YS"],"funding":["National Taiwan University Hospital","Ministry of Education","National Taiwan University","National Health Research Institutes","Academia Sinica","National Science and Technology Council","Kaohsiung Veterans General Hospital"],"pagination":["e20220727"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10174191"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["220(8)"],"pubmed_abstract":["Type I interferons are important antiviral cytokines, but prolonged interferon production is detrimental to the host. The TLR3-driven immune response is crucial for mammalian antiviral immunity, and its intracellular localization determines induction of type I interferons; however, the mechanism terminating TLR3 signaling remains obscure. Here, we show that the E3 ubiquitin ligase ZNRF1 controls TLR3 sorting into multivesicular bodies/lysosomes to terminate signaling and type I interferon production. Mechanistically, c-Src kinase activated by TLR3 engagement phosphorylates ZNRF1 at tyrosine 103, which mediates K63-linked ubiquitination of TLR3 at lysine 813 and promotes TLR3 lysosomal trafficking and degradation. ZNRF1-deficient mice and cells are resistant to infection by encephalomyocard"],"journal":["The Journal of experimental medicine"],"pubmed_title":["The Src-ZNRF1 axis controls TLR3 trafficking and interferon responses to limit lung barrier damage."],"pmcid":["PMC10174191"],"funding_grant_id":["109-2327-B-002-009","NTU-CC-111L893903","110-2634-F-002-044","AS-CFII-108-104","ASCFII-108-104","111C101-7","108-2320-B-002-020-MY3","KSVGH110-025","109-2314-B-002-080","110L901402B","NHRI-EX110-11031SI","109-2320-B-002-018-MY3","110-2740-B-002-006","ASIA-106-L04"],"pubmed_authors":["Tsai CY","Ho YH","Tsai YM","Lin YS","Chao TL","Lai TY","Lee CY","Jhuang SJ","Hsu LC","Chang SY","Hsueh YP","Chang YC","Chen CY","Chuang TH","Liu YL"],"additional_accession":[]},"is_claimable":false,"name":"The Src-ZNRF1 axis controls TLR3 trafficking and interferon responses to limit lung barrier damage.","description":"Type I interferons are important antiviral cytokines, but prolonged interferon production is detrimental to the host. The TLR3-driven immune response is crucial for mammalian antiviral immunity, and its intracellular localization determines induction of type I interferons; however, the mechanism terminating TLR3 signaling remains obscure. Here, we show that the E3 ubiquitin ligase ZNRF1 controls TLR3 sorting into multivesicular bodies/lysosomes to terminate signaling and type I interferon production. Mechanistically, c-Src kinase activated by TLR3 engagement phosphorylates ZNRF1 at tyrosine 103, which mediates K63-linked ubiquitination of TLR3 at lysine 813 and promotes TLR3 lysosomal trafficking and degradation. ZNRF1-deficient mice and cells are resistant to infection by encephalomyocard","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Aug","modification":"2026-07-15T01:42:19.055Z","creation":"2025-04-05T21:09:00.33Z"},"accession":"S-EPMC10174191","cross_references":{"pubmed":["37158982"],"doi":["10.1084/jem.20220727"]}}