{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/482"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/482","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Key Role of Lys63-Linked Polyubiquitination in Viral Activation of IRF3","abstract":"Viral nucleic acids exposed during invasion and proliferation are detected by mammalian cells through receptors belonging to pattern-recognition receptors family (PRRs). Among PRRs, RIG-I-like receptors (RLRs), including RIG-I, MDA5 and LGP2, are responsible for sensing intracellular viral RNAs. MAVS, a mitochondria-localized transmembrane protein, transduces signaling from RIG-I and MDA5 to activate downstream transcription factors IRF3 and NF-kB, which contribute to the induction of IFNb. Despite growing list of components revealed in RIG-I/MAVS/IRF3 pathway, molecular mechanism by which MAVS activates IRF3 upon viral infection has remained largely unclear. In current study, employing a cell-free system together with conventional fractionation procedures, Ubc5 was identified as a specific ubiquitin-conjugating enzyme (E2) involved in IRF3 activation. Taking advantages of inducible-RNAi strategy, catalytically active Ubc5 was shown to be essential for viral activation of IRF3. Furthermore, evidences were obtained indicating that Lys63-linked polyubiquitination played a key role in MAVS-mediated IRF3 activation both in vitro and in vivo. Finally, NEMO was demonstrated to function as a ubiquitin-chain adaptor recruiting and activating TBK1, the kinase for IRF3 phosphorylation. Those results offered insights into the mechanism underlying IRF3 activation mediated by K63-linked polyubiquitination.","abstract_html":"Viral nucleic acids exposed during invasion and proliferation are detected by mammalian cells through receptors belonging to pattern-recognition receptors family (PRRs). Among PRRs, RIG-I-like receptors (RLRs), including RIG-I, MDA5 and LGP2, are responsible for sensing intracellular viral RNAs. MAVS, a mitochondria-localized transmembrane protein, transduces signaling from RIG-I and MDA5 to activate downstream transcription factors IRF3 and NF-kB, which contribute to the induction of IFNb. Despite growing list of components revealed in RIG-I/MAVS/IRF3 pathway, molecular mechanism by which MAVS activates IRF3 upon viral infection has remained largely unclear. In current study, employing a cell-free system together with conventional fractionation procedures, Ubc5 was identified as a specific ubiquitin-conjugating enzyme (E2) involved in IRF3 activation. Taking advantages of inducible-RNAi strategy, catalytically active Ubc5 was shown to be essential for viral activation of IRF3. Furthermore, evidences were obtained indicating that Lys63-linked polyubiquitination played a key role in MAVS-mediated IRF3 activation both in vitro and in vivo. Finally, NEMO was demonstrated to function as a ubiquitin-chain adaptor recruiting and activating TBK1, the kinase for IRF3 phosphorylation. Those results offered insights into the mechanism underlying IRF3 activation mediated by K63-linked polyubiquitination.","abstract_has_math":false,"creators":["Zeng, Wenwen"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Chen, Zhijian J."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2010,"date_issued":"2010-07-12T18:13:16Z","date_published":"2010-07-12T18:13:16Z","updated_at":"2026-07-24T05:52:17Z","subjects":["Interferon Regulatory Factor-3","Sendai virus","Virus Activation","Ubiquitin-Conjugating Enzymes"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["754805403"],"render_values":[{"text":"754805403","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/482","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Chen, Zhijian J."]},{"key":"dc:creator","label":"Author","values":["Zeng, Wenwen"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2010-07-12T18:13:16Z","2009-06-19"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","Text","dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Interferon Regulatory Factor-3","Sendai virus","Virus Activation","Ubiquitin-Conjugating Enzymes"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/482","754805403"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Viral nucleic acids exposed during invasion and proliferation are detected by mammalian cells through receptors belonging to pattern-recognition receptors family (PRRs). Among PRRs, RIG-I-like receptors (RLRs), including RIG-I, MDA5 and LGP2, are responsible for sensing intracellular viral RNAs. MAVS, a mitochondria-localized transmembrane protein, transduces signaling from RIG-I and MDA5 to activate downstream transcription factors IRF3 and NF-kB, which contribute to the induction of IFNb. Despite growing list of components revealed in RIG-I/MAVS/IRF3 pathway, molecular mechanism by which MAVS activates IRF3 upon viral infection has remained largely unclear. In current study, employing a cell-free system together with conventional fractionation procedures, Ubc5 was identified as a specific ubiquitin-conjugating enzyme (E2) involved in IRF3 activation. Taking advantages of inducible-RNAi strategy, catalytically active Ubc5 was shown to be essential for viral activation of IRF3. Furthermore, evidences were obtained indicating that Lys63-linked polyubiquitination played a key role in MAVS-mediated IRF3 activation both in vitro and in vivo. Finally, NEMO was demonstrated to function as a ubiquitin-chain adaptor recruiting and activating TBK1, the kinase for IRF3 phosphorylation. Those results offered insights into the mechanism underlying IRF3 activation mediated by K63-linked polyubiquitination."]},{"key":"dc:format","label":"Dc Format","values":["Electronic","application/pdf","born digital"]},{"key":"dc:title","label":"Title","values":["Key Role of Lys63-Linked Polyubiquitination in Viral Activation of IRF3"]}]}],"canonical_facts":{"dc:contributor":["Chen, Zhijian J."],"dc:creator":["Zeng, Wenwen"],"dc:date":["2010-07-12T18:13:16Z","2009-06-19"],"dc:description":["Viral nucleic acids exposed during invasion and proliferation are detected by mammalian cells through receptors belonging to pattern-recognition receptors family (PRRs). Among PRRs, RIG-I-like receptors (RLRs), including RIG-I, MDA5 and LGP2, are responsible for sensing intracellular viral RNAs. MAVS, a mitochondria-localized transmembrane protein, transduces signaling from RIG-I and MDA5 to activate downstream transcription factors IRF3 and NF-kB, which contribute to the induction of IFNb. Despite growing list of components revealed in RIG-I/MAVS/IRF3 pathway, molecular mechanism by which MAVS activates IRF3 upon viral infection has remained largely unclear. In current study, employing a cell-free system together with conventional fractionation procedures, Ubc5 was identified as a specific ubiquitin-conjugating enzyme (E2) involved in IRF3 activation. Taking advantages of inducible-RNAi strategy, catalytically active Ubc5 was shown to be essential for viral activation of IRF3. Furthermore, evidences were obtained indicating that Lys63-linked polyubiquitination played a key role in MAVS-mediated IRF3 activation both in vitro and in vivo. Finally, NEMO was demonstrated to function as a ubiquitin-chain adaptor recruiting and activating TBK1, the kinase for IRF3 phosphorylation. Those results offered insights into the mechanism underlying IRF3 activation mediated by K63-linked polyubiquitination."],"dc:format":["Electronic","application/pdf","born digital"],"dc:identifier":["https://hdl.handle.net/2152.5/482","754805403"],"dc:language":["en"],"dc:subject":["Interferon Regulatory Factor-3","Sendai virus","Virus Activation","Ubiquitin-Conjugating Enzymes"],"dc:title":["Key Role of Lys63-Linked Polyubiquitination in Viral Activation of IRF3"],"dc:type":["Thesis","Text","dissertation"]},"updated_at":"2026-07-24T05:52:17Z"}