Related Experiment Video
Updated: Jun 28, 2025

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
Published on: July 26, 2017
The TRIF-RIPK1-Caspase-8 signalling in the regulation of TLR4-driven gene expression
Chengyang Zhang1, Yang Zhou1, Shuangtong Xi1
1Department of Biochemistry and molecular biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
Abstract:
The inflammatory response is tightly regulated to eliminate invading pathogens and avoid excessive production of inflammatory mediators and tissue damage. Caspase-8 is a cysteine protease that is involved in programmed cell death. Here we show the TRIF-RIPK1-Caspase-8 is required for LPS-induced CYLD degradation in macrophages. TRIF functions in the upstream of RIPK1. The homotypic interaction motif of TRIF and the death domain of RIPK1 are essential for Caspase-8 activation. Caspase-8 cleaves CYLD and the D235A mutant is resistant to the protease activity of Caspase-8. TRIF and RIPK1 serve as substrates of Capase-8 in vitro. cFLIP interacts with Caspase-8 to modulate its protease activity on CYLD and cell death. Deficiency in TRIF, Caspase-8 or CYLD can lead to a decrease or increase in the expression of genes encoding inflammatory cytokines. Together, the TRIF-Caspase-8 and CYLD play opposite roles in the regulation of TLR4 signalling.
More Related Videos
Related Concept Videos
MAPK Signaling Cascades
Regulation of the Unfolded Protein Response
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
The Extrinsic Apoptotic Pathway
The JAK-STAT Signaling Pathway
Amplifying Signals via Enzymatic Cascade

