Related Experiment Video
Updated: Jun 22, 2026

A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
The E3 ubiquitin ligase Nrdp1 'preferentially' promotes TLR-mediated production of type I interferon
Chen Wang1, Taoyong Chen, Jia Zhang
1National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China.
Abstract:
E3 ubiquitin ligases are important in both innate and adaptive immunity. Here we report that Nrdp1, an E3 ubiquitin ligase, inhibited the production of proinflammatory cytokines but increased interferon-beta production in Toll-like receptor-triggered macrophages by suppressing adaptor MyD88-dependent activation of transcription factors NF-kappaB and AP-1 while promoting activation of the kinase TBK1 and transcription factor IRF3. Nrdp1 directly bound and polyubiquitinated MyD88 and TBK1, which led to degradation of MyD88 and activation of TBK1. Knockdown of Nrdp1 inhibited the degradation of MyD88 and the activation of TBK1 and IRF3. Nrdp1-transgenic mice showed resistance to lipopolysaccharide-induced endotoxin shock and to infection with vesicular stomatitis virus. Our data suggest that Nrdp1 functions as both an adaptor protein and an E3 unbiquitin ligase to regulate TLR responses in different ways.
Related Concept Videos
Regulation of the Unfolded Protein Response
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The Unfolded Protein Response
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Regulation of Nuclear Protein Sorting

