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dc.contributor.advisorChen, Zhijian J.en
dc.creatorZeng, Wenwenen
dc.date.accessioned2010-07-12T18:13:16Zen
dc.date.available2010-07-12T18:13:16Zen
dc.date.issued2009-06-19
dc.identifier.urihttp://hdl.handle.net/2152.5/482
dc.description.abstractViral 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.en
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.language.isoenen
dc.subjectInterferon Regulatory Factor-3en
dc.subjectSendai virusen
dc.subjectVirus Activationen
dc.subjectUbiquitin-Conjugating Enzymesen
dc.titleKey Role of Lys63-Linked Polyubiquitination in Viral Activation of IRF3en
dc.typeThesisen
dc.type.materialTexten
dc.type.genredissertationen
dc.format.digitalOriginborn digitalen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.nameDoctor of Philosophyen
thesis.degree.levelDoctoralen
thesis.degree.disciplineGenetics and Developmenten
thesis.date.available2011-06-19
dc.identifier.oclc754805403


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