Table of Contents
What is the Fas pathway?
The Fas cell signaling pathway has a central role in the physiological regulation of programmed cell death (also called apoptosis) and has been implicated in the pathogenesis of various malignancies and diseases of the immune system.
What is FAS on T cells?
Fas ligand or FasL is a homotrimeric type II transmembrane protein expressed on cytotoxic T lymphocytes. It signals through trimerization of FasR, which spans the membrane of the “target” cell. This trimerization usually leads to apoptosis, or cell death.
What does the Fas receptor do?
The Fas receptor is a death receptor on the surface of cells that leads to programmed cell death (apoptosis) if it binds its ligand, Fas ligand (FasL). It is one of two apoptosis pathways, the other being the mitochondrial pathway.
What activates Fas ligand?
Fas ligand (expressed on activated T cells) binding to Fas (CD95) stimulates a signaling pathway resulting in apoptotic death of the Fas-expressing cell. Fas-induced apoptosis of activated cells contributes to the elimination of autoreactive B and T lymphocytes.
What cells express Fas receptors?
Similar to TNF, the physiological ligand for Fas (CD95L or FasL) is synthesized as a type II membrane protein and is expressed on activated B cells, T cells, and NK cells.
Do T cells have FAS or FasL?
Moreover, the Fas–FasL pathway is required not only for death of T cells (43) but also for deletion of autoreactive B cells (44, 45), B cell somatic hypermutation (46), cytotoxicity of NK and CD8 T cells (47, 48), apoptosis of endothelial cells (49), regulation of myeloid suppressor cells’ turnover (50), and activation …
How does Fas mediated apoptosis work?
Fas-mediated apoptosis proceeds through the extrinsic pathway via the binding to their respective receptors of ligands, such as FasL, tumor necrosis factor-alpha (TNF-α), lymphotoxin-alpha (LT-α), TNF-like protein-1A (TL1A), and Apo2L/TNF-related apoptosis-inducing ligand (TRAIL) (Figure 1).
What is Fas Fas ligand interaction?
The Fas/FasL interaction is a common effector mechanism of β-cell apoptosis and islet injury under inflammatory conditions, and physiological modulation of immune homeostasis, including control of aberrant autoimmune reactions.
Do all cells express FAS?
Fas, which belongs to the TNF-R family, is expressed in lymphoid, myeloid, and nonhematopoietic cell types, while FasL is primarily expressed in CD8+ or activated CD4+ T cells.
Do T cells express Fas receptors?
The Fas receptor is widely expressed in cells of the immune system including T cells, B cells, and monocytes [6, 32].
How does Fas ligand induce apoptosis?
The induction of apoptosis is triggered by the interaction of Fas with its ligand (FasL), a 40-kDa membrane protein (14) allowing recruitment of the adaptor protein Fas-associated death domain (FADD) (15) and binding of procaspase-8, resulting in the formation of the death-inducing signaling complex (DISC) (16, 17).
Which cells express FAS?
In particular, FasL is expressed by astrocytes, oligodendrocytes, and macrophages, while Fas is mainly expressed by macrophages, T cells, and oligodendrocytes (69, 70). Several studies have addressed the role of the Fas–FasL system in experimental autoimmune encephalomyelitis (EAE), the murine model of MS (71–75).
What happens when the FAS protein binds to a receptor on a cell?
Interaction between surface-bound Fas receptor with its ligand (FasL) activates caspase-8, which in turn activates downstream effector caspases that are necessary for apoptosis.
How does FAS mediated apoptosis work?
What is the FAS cell signaling pathway?
The Fas cell signaling pathway has a central role in the physiological regulation of programmed cell death (also called apoptosis) and has been implicated in the pathogenesis of various malignancies and diseases of the immune system.
How does the Fas receptor induce apoptosis?
The Fas receptor induces an apoptotic signal by binding to FasL expressed on the surface of other cells. Fas is a Type-I transmembrane protein, whereas FasL a Type-II transmembrane protein of TNF family and can be shed in a soluble form by action of metalloproteinase ( 1 ).
Do FAS and FasL interactions affect thymine levels in colon cancer cells?
Since, Fas and FasL are known regulators of apoptosis in cells of the immune system, blocking Fas/FasL interactions in human colon carcinoma cells can lead to thymine less death.
Is the FAS – FASL pathway involved in the pathogenesis of lupus?
Dysregulation of apoptosis, particularly in the Fas – FasL pathway, is considered to be involved in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Watanabe-Fukunaga et al., (1992) demonstrated that MRL/lpr mice carrying the lymphoproliferation ( lpr) mutation have defects in the Fas gene.