Related Experiment Video

Updated: Jun 21, 2026

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
09:51

Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling

Published on: July 26, 2017

Regulation of TNFRSF and innate immune signalling complexes by TRAFs and cIAPs

J Silke1, R Brink

  • 1Department of Biochemistry, La Trobe University, Kingsbury Drive, Melbourne, Victoria 3086, Australia. j.silke@latrobe.edu.au

Cell Death and Differentiation
|August 15, 2009
PubMed

Insights

Inhibitors of apoptosis (IAPs) and TNF receptor-associated factors (TRAFs) regulate signaling in the TNF receptor superfamily (TNFRSF) and innate immunity. This review focuses on TNFRSF members without death domains and the roles of TRAFs and IAPs in these pathways.

Area of Science:

  • Cellular Biology
  • Immunology
  • Molecular Biology

Background:

  • Inhibitors of apoptosis (IAPs) and TNF receptor-associated factors (TRAFs) are key regulators of cell signaling.
  • These proteins play crucial roles in the TNF receptor superfamily (TNFRSF) and innate immune pathways.
  • Recent discoveries highlight their expanding influence beyond canonical TNFRSF signaling.

Purpose of the Study:

  • To review the roles of TRAFs and IAPs in regulating signaling from death domain-lacking TNFRSF members.
  • To explore the speculative roles of IAPs and TRAFs in innate immune signaling.
  • To consolidate current understanding and identify future research directions in these areas.

Main Methods:

  • Literature review and synthesis of existing research.
  • Focus on signaling pathways involving TRAF2, TRAF3, and cIAPs.
  • Analysis of studies examining TNFRSF members without death domains.
  • Exploration of data related to innate immune signaling.

Main Results:

  • TRAFs and IAPs are critical for signaling initiated by specific TNFRSF members.
  • Their functions extend to regulating pathways within the innate immune system.
  • The precise mechanisms in innate immunity are still under investigation but show significant promise.

Conclusions:

  • IAPs and TRAFs are versatile regulators with established roles in TNFRSF signaling and emerging importance in innate immunity.
  • Further research is needed to fully elucidate their functions, particularly in the context of innate immune responses.
  • Understanding these pathways can lead to novel therapeutic strategies for immune-related diseases.

More Related Videos

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin10:21

Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin

Published on: September 12, 2019

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
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...