Fas Ligand (FasL)

Fas Ligand (FasL; FASLG; CD95L), is a ligand for TNFRSF6/FAS belonging to the tumor necrosis factor (TNF). It is a type II transmembrane protein, riggering apoptosis of lymphocytes^[1]. FasL is expressed on a variety of cell types, including T cells, natural killer (NK) cells, monocytes, neutrophils, breast epithelial cells, and vascular endothelial cells^[2]. FasL exerts different biological activity by cleaved into 4 isoforms including membrane form, soluble form, ADAM10-processed FasL form (APL) and SPPL2A-processed FasL form (SPA). Among them, the membrane-bound form and a soluble form generated by proteolytic action of matrix metalloproteinases (MMP)^[2]. FasL or soluble FasL binding to Fas results in receptor aggregation and in the interaction of a protein called Fas-associated death domain with the Fas cytoplasmic tail. The interaction triggers a cascade of intracellular events, including the activation of the IL-1-converting enzyme-like cysteine protease (caspase 8), that ultimately leads to nucleoprotein cleavage, DNA fragmentation, and cell apoptosis^[3]. The loss of function due to mutations in murine FasL, murine Fas, human Fas, or human FasL leads to lymphoproliferation, lymphadenopathy, and autoimmune diseases^[1][4]. Meanwhile, defective activation-induced cell death (AICD) results in spontaneous mutation of Fas and FasL genes in mice with lupus-like autoimmune disease^[3]. Human Fas Ligand also involves in Jurkat cell apoptosis and binds TNFRSF6B/DcR3 to bolck apoptosis, which is a decoy receptor of apoptosis termination^[2].

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