Summary
Basic Information
Immunogen
NS0-derived recombinant mouse Fas Ligand/TNFSF6, Pro132-Leu279, Accession # P41047
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.
Formulations & Storage [For reference only, actual COA shall prevail!]
Buffer
A saline solution, BSA
Preservative
0.05% sodium azide
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freeze/thaw cycles.
Target
Introduction
Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells. May be involved in cytotoxic T-cell mediated apoptosis and in T-cell development. TNFRSF6/FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both. Binding to the decoy receptor TNFRSF6B/DcR3 modulates its effects.
Alternative Names
Fas Ligand; Fas Ligand (TNF Superfamily, Member 6); Apoptosis Antigen Ligand; Fas Antigen Ligand; CD95 Ligand; APT1LG1; TNFSF6; CD95-L; CD95L; APTL; FASL;
Research Area
Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells (PubMed:26334989, PubMed:9228058).
Involved in cytotoxic T-cell-mediated apoptosis, natural killer cell-mediated apoptosis and in T-cell development (PubMed:9228058, PubMed:7528780, PubMed:9427603).
Initiates fratricidal/suicidal activation-induced cell death (AICD) in antigen-activated T-cells contributing to the termination of immune responses (By similarity).
TNFRSF6/FAS-mediated apoptosis has also a role in the induction of peripheral tolerance (By similarity).
Binds to TNFRSF6B/DcR3, a decoy receptor that blocks apoptosis (PubMed:27806260).
Tumor necrosis factor ligand superfamily member 6, soluble form:
Induces FAS-mediated activation of NF-kappa-B, initiating non-apoptotic signaling pathways (By similarity).
Can induce apoptosis but does not appear to be essential for this process (PubMed:27806260).
FasL intracellular domain:
Cytoplasmic form induces gene transcription inhibition.
Biological Process
Activation of cysteine-type endopeptidase activity involved in apoptotic process Source: BHF-UCL
Apoptotic process Source: ProtInc
Apoptotic signaling pathway Source: BHF-UCL
Cell-cell signaling Source: ProtInc
Cellular chloride ion homeostasis Source: Ensembl
Cellular response to interferon-gamma Source: Ensembl
Endosomal lumen acidification Source: Ensembl
Extrinsic apoptotic signaling pathway Source: UniProtKB
Extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
Inflammatory cell apoptotic process Source: Ensembl
Necroptotic process Source: BHF-UCL
Necroptotic signaling pathway Source: BHF-UCL
Negative regulation of angiogenesis Source: BHF-UCL
Negative regulation of transcription by RNA polymerase II Source: UniProtKB
Positive regulation of apoptotic process Source: UniProtKB
Positive regulation of cell population proliferation Source: Ensembl
Positive regulation of endothelial cell apoptotic process Source: BHF-UCL
Positive regulation of epidermal growth factor receptor signaling pathway Source: Ensembl
Positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
Positive regulation of neuron apoptotic process Source: Ensembl
Positive regulation of phosphatidylserine exposure on apoptotic cell surface Source: UniProtKB
Release of sequestered calcium ion into cytosol by endoplasmic reticulum Source: MGI
Response to growth factor Source: Ensembl
Response to lipopolysaccharide Source: Ensembl
Retinal cell programmed cell death Source: Ensembl
Signal transduction Source: ProtInc
T cell apoptotic process Source: UniProtKB
Cellular Location
Lysosome lumen; Cell membrane; Cytoplasmic vesicle lumen. Is internalized into multivesicular bodies of secretory lysosomes after phosphorylation by FGR and monoubiquitination (PubMed:17164290). Colocalizes with the SPPL2A protease at the cell membrane (PubMed:17557115).
Tumor necrosis factor ligand superfamily member 6, soluble form: Secreted. May be released into the extracellular fluid by cleavage from the cell surface.
FasL intracellular domain: Nucleus. The FasL ICD cytoplasmic form is translocated into the nucleus.
Involvement in disease
Autoimmune lymphoproliferative syndrome 1B (ALPS1B):
A disorder of apoptosis that manifests in early childhood and results in the accumulation of autoreactive lymphocytes. It is characterized by non-malignant lymphadenopathy with hepatosplenomegaly, and autoimmune hemolytic anemia, thrombocytopenia and neutropenia.
Topology
Cytoplasmic: 1-80
Helical: 81-102
Extracellular: 103-281
PTM
The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form undergoes two successive intramembrane proteolytic cleavages. The first one is processed by ADAM10 producing an N-terminal fragment, which lacks the receptor-binding extracellular domain. This ADAM10-processed FasL (FasL APL) remnant form is still membrane anchored and further processed by SPPL2A that liberates the FasL intracellular domain (FasL ICD). FasL shedding by ADAM10 is a prerequisite for subsequent intramembrane cleavage by SPPL2A in T-cells.
N-glycosylated (PubMed:9228058). Glycosylation enhances apoptotic activity (PubMed:27806260).
Phosphorylated by FGR on tyrosine residues; this is required for ubiquitination and subsequent internalization.
Monoubiquitinated.