Related Experiment Videos
Tumor necrosis factor receptor and Fas signaling mechanisms
D Wallach1, E E Varfolomeev, N L Malinin
1Department of Biological Chemistry, Weizmann Institute, Rehovot, Israel. lvwalach@weizmann.weizmann.ac.il
Abstract:
Four members of the tumor necrosis factor (TNF) ligand family, TNF-alpha, LT-alpha, LT-beta, and LIGHT, interact with four receptors of the TNF/nerve growth factor family, the p55 TNF receptor (CD120a), the p75 TNF receptor (CD120b), the lymphotoxin beta receptor (LT beta R), and herpes virus entry mediator (HVEM) to control a wide range of innate and adaptive immune response functions. Of these, the most thoroughly studied are cell death induction and regulation of the inflammatory process. Fas/Apo1 (CD95), a receptor of the TNF receptor family activated by a distinct ligand, induces death in cells through mechanisms shared with CD120a. The last four years have seen a proliferation in knowledge of the proteins participating in the signaling by the TNF system and CD95. The downstream signaling molecules identified so far--caspases, phospholipases, the three known mitogen activated protein (MAP) kinase pathways, and the NF-kappa B activation cascade--mediate the effects of other inducers as well. However, the molecules that initiate these signaling events, including the death domain- and TNF receptor associated factor (TRAF) domain-containing adapter proteins and the signaling enzymes associated with them, are largely unique to the TNF/nerve growth factor receptor family.
Insights
Tumor Necrosis Factor (TNF) ligands and receptors regulate immune responses, including cell death and inflammation. Signaling pathways involve unique adapter proteins specific to the TNF/nerve growth factor receptor family.
Area of Science:
- Immunology
- Molecular Biology
- Cell Signaling
Background:
- The tumor necrosis factor (TNF) ligand family and TNF/nerve growth factor receptor family are crucial for immune responses.
- Key functions include cell death induction and inflammatory process regulation.
- Recent advances have expanded knowledge of signaling proteins within the TNF system and Fas/Apo1 (CD95) pathways.
Purpose of the Study:
- To review the current understanding of TNF superfamily signaling pathways.
- To highlight the unique adapter proteins initiating signaling events in the TNF/nerve growth factor receptor family.
Main Methods:
- Literature review of recent findings on TNF and CD95 signaling.
- Analysis of known downstream signaling molecules and initiating adapter proteins.
Main Results:
- TNF ligands (TNF-alpha, LT-alpha, LT-beta, LIGHT) interact with receptors (p55 TNF receptor, p75 TNF receptor, LT beta R, HVEM).
- Downstream signaling involves caspases, phospholipases, MAP kinase pathways, and NF-kappa B.
- Adapter proteins with death and TNF Receptor Associated Factor (TRAF) domains are critical initiators and are largely unique to this receptor family.
Conclusions:
- The TNF/nerve growth factor receptor family utilizes distinct adapter proteins to initiate signaling cascades.
- Understanding these unique initiating molecules is key to comprehending innate and adaptive immune regulation.