Chapter category: Signal Transduction
FasL-Independent Activation of Fas
Fas Signaling
Edited by: Harald WajantISBN: 0-387-32172-1
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Chapter authors:
Faustino Mollinedo and Consuelo Gajate
Fas death receptor (also named CD95 or APO-1) is physiologically activated through binding to its cognate ligand, FasL. Fas/FasL interaction induces oligomerization and aggregation of Fas receptor, leading eventually to apoptosis after protein-protein interactions with adaptor and effector proteins. However, recent evidences demonstrate that either oligomerization of the receptor in trimers, as well as Fas aggregation in large clusters do not require its interaction with FasL. Activation of Fas through its translocation into membrane rafts, forming Fas caps, can be rendered independently of FasL. This FasL-independent cocapping of Fas in membrane rafts generates high local concentrations of Fas, providing scaffolds for coupling adaptor and effector proteins involved in Fas signaling. Thus, Fas receptor can be modulated either extracellularly, via FasL, or intracellularly independently of its ligand. Unraveling the molecular mechanism involved in FasL-independent activation of Fas will raise putative novel therapeutic interventions, especially in disorders where apoptosis is deficient such as cancer and autoimmune diseases, avoiding in this way the deleterious side effects that preclude the use of systemic activation of the Fas receptor by its ligand.
Additional chapters from this book:
The FasL-Fas System in Disease and Therapy
Harald Wajant and Frank Henkler
The physiological roles of the FasL-Fas system include apoptosis-related processes like tumor surveillance, elimination of virus infected cells or deletion of autoreactive T- and B-cells. In recent ...
Fas-More Than an Apoptosis Inducer
Harald Wajant
Fas (Apo-1 or CD95) and its corresponding ligand FasL (CD95L) are representative members of the TNF receptor and TNF ligand family that have been implicated in a variety of apoptotic processes, invo...
FasL and Fas: Typical Members of the TNF Ligand and Receptor Family
Anja Krippner-Heidenreich and Peter Scheurich
The membrane receptor Fas is one of the central members of the TNF receptor superfamily, representing the prototype of an apoptosis inducer. Its cognate ligand, FasL, is expressed as a type II trans...
Fas Induced Necrosis
Tom Vanden Berghe, Nele Festjens, Michael Kalai, Xavier Saelens and Peter Vandenabeele
Fas/CD95 is an important regulator of cell death in development and homeostasis of the immune system. Apoptosis is the most frequently observed type of cell death induced by Fas. It is characterized...
Retrograde Fas Ligand Signaling
A. Linkermann, J. Qian and O. Janssen
As highlighted in the previous chapters, the interaction of Fas with Fas Ligand (FasL) affects many different aspects related to activation and apoptosis of Fas-expressing immune and tumor cells. Ov...
Fas-Activation, Development and Homeostasis of T Cells
Georg Hacker
Fas (APO-1/CD95) is found on various cells of the immune system where its expression depends on differentiation and activation status of the cells. Analysis of the function of Fas on T lymphocytes h...
FasL and Fas in Liver Homeostasis and Hepatic Injuries
Maria Eugenia Guicciardi and Gregory J. Gores
Fas is a death receptor expressed by every cell type in the liver. Engagement of Fas with its cognate ligand, Fas ligand (FasL), initiates a signaling cascade resulting in cell death by apoptosis. F...
Role of Ceramide in CD95 Signaling
Volker Teichgr?ber, Gabriele Hessler and Erich Gulbins
Recent studies indicate that the reorganization of receptor molecules in distinct domains of the cell membrane constitutes an important and general mechanism that is required for the initiation of s...
FasL-Independent Activation of Fas
Faustino Mollinedo and Consuelo Gajate
Fas death receptor (also named CD95 or APO-1) is physiologically activated through binding to its cognate ligand, FasL. Fas/FasL interaction induces oligomerization and aggregation of Fas receptor, ...
Tools for Activation and Neutralization of Fas Signaling
Pascal Schneider
Apoptosis mediated by the Fas / FasL pair of receptor and ligand is involved in physiological or pathological processes in which cell death is either required to eliminate potentially harmful infect...
Regulation of Fas Signaling by FLIP Proteins
Margot Thome
Fas is a member of the tumor necrosis factor receptor family that can induce apoptosis by the recruitment and activation of caspase-8 (formerly called FLICE, MACH or MCH-5). Recently, caspase-8/FLIC...
