Death the Fas way: regulation and pathophysiology of CD95 and its ligand

Apoptotic cell death mediated by the members of the tumor necrosis factor r eceptor family is an essential process involved in the regulation of cellul ar homeostasis during development, differentiation, and pathophysiological conditions. Among the cell death receptors comprising the tumor necrosis fa ctor receptor superfamily, CD95/APO-1 (Fas) is the best characterized. The specific interaction of Fas with its cognate ligand, Fas ligand (FasL), eli cits the activation of a death-inducing caspase (cysteine aspartic acid pro teases) cascade, occurring in a transcription-independent manner. Caspase a ctivation executes the apoptosis process by cleaving various intracellular substrates, leading to genomic DNA fragmentation, cell membrane blebbing, a nd the exposure of phagocytosis signaling molecules on the cell surface. Re cent studies have shown that the Fas/FasL pathway plays an important role i n regulating the life and death of the immune system through activation-ind uced cell death. In addition, these molecules have been implicated in aging , human immunodeficiency virus infection, drug abuse, stress, and cancer de velopment. In this review, we will focus on the mechanisms that regulate Fa s and FasLexpression, and how their deregulation leads to diseases. (C) 200 1 Elsevier Science Inc. All rights reserved.