Key Role of Lys63-Linked Polyubiquitination in Viral Activation of IRF3

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Title: Key Role of Lys63-Linked Polyubiquitination in Viral Activation of IRF3
Author: Zeng, Wenwen
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 .
URI: http : / /hdl .handle .net /2152 .5 /482
Date: 2009-06-19

Citation

Key Role of Lys63-Linked Polyubiquitination in Viral Activation of IRF3. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /482 .

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