Related Experiment Video
Updated: Mar 21, 2026

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
Ubiquitination of the Transcription Factor IRF-3 Activates RIPA, the Apoptotic Pathway that Protects Mice from Viral
Saurabh Chattopadhyay1, Teodora Kuzmanovic2, Ying Zhang2
1Department of Molecular Genetics, Cleveland Clinic, Cleveland, OH 44195, USA; Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, 3000 Arlington Avenue, Mailstop 1021, Toledo, OH 43614, USA.
Abstract:
The transcription factor IRF-3 mediates cellular antiviral response by inducing the expression of interferon and other antiviral proteins. In RNA-virus infected cells, IRF-3's transcriptional activation is triggered primarily by RIG-I-like receptors (RLR), which can also activate the RLR-induced IRF-3-mediated pathway of apoptosis (RIPA). Here, we have reported that the pathway of IRF-3 activation in RIPA was independent of and distinct from the known pathway of transcriptional activation of IRF-3. It required linear polyubiquitination of two specific lysine residues of IRF-3 by LUBAC, the linear polyubiquitinating enzyme complex, which bound IRF-3 in signal-dependent fashion. To evaluate the role of RIPA in viral pathogenesis, we engineered a genetically targeted mouse, which expressed a mutant IRF-3 that was RIPA-competent but transcriptionally inert; this single-action IRF-3 could protect mice from lethal viral infection. Our observations indicated that IRF-3-mediated apoptosis of virus-infected cells could be an effective antiviral mechanism, without expression of the interferon-stimulated genes.
More Related Videos
09:15Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells
Published on: October 20, 2022
08:15Generation of a RIP1 Knockout U937 Cell Line Using the CRISPR-Cas9 System
Published on: April 11, 2025
Related Concept Videos
Regulation of the Unfolded Protein Response
Experimental RNAi
PI3K/mTOR/AKT Signaling Pathway
The Extrinsic Apoptotic Pathway
The Unfolded Protein Response
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...