title: Death the Fas way: regulation and pathophysiology of CD95 and its ligand.
abstract: Apoptotic cell death mediated by the members of the tumor necrosis factor receptor family is an essential process involved in the regulation of cellular homeostasis during development, differentiation, and pathophysiological conditions. Among the cell death receptors comprising the tumor necrosis factor receptor superfamily, CD95/APO-1 (Fas) is the best characterized. The specific interaction of Fas with its cognate ligand, Fas ligand (FasL), elicits the activation of a death-inducing caspase (cysteine aspartic acid proteases) cascade, occurring in a transcription-independent manner. Caspase activation executes the apoptosis process by cleaving various intracellular substrates, leading to genomic DNA fragmentation, cell membrane blebbing, and the exposure of phagocytosis signaling molecules on the cell surface. Recent studies have shown that the Fas/FasL pathway plays an important role in regulating the life and death of the immune system through activation-induced cell death. In addition, these molecules have been implicated in aging, human immunodeficiency virus infection, drug abuse, stress, and cancer development. In this review, we will focus on the mechanisms that regulate Fas and FasL expression, and how their deregulation leads to diseases.
authors.affiliation: Department of Immunology, Holland Laboratory, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855, USA.
authors.forename: K
authors.initials: K
authors.lastname: Sharma
authors.forename: R X
authors.initials: RX
authors.lastname: Wang
authors.forename: L Y
authors.initials: LY
authors.lastname: Zhang
authors.forename: D L
authors.initials: DL
authors.lastname: Yin
authors.forename: X Y
authors.initials: XY
authors.lastname: Luo
authors.forename: J C
authors.initials: JC
authors.lastname: Solomon
authors.forename: R F
authors.initials: RF
authors.lastname: Jiang
authors.forename: K
authors.initials: K
authors.lastname: Markos
authors.forename: W
authors.initials: W
authors.lastname: Davidson
authors.forename: D W
authors.initials: DW
authors.lastname: Scott
authors.forename: Y F
authors.initials: YF
authors.lastname: Shi
mesh_terms: D000375:Aging; D001008:Anxiety Disorders; D017209:Apoptosis; D001768:Blister; D002462:Cell Membrane; D004249:DNA Damage; D053222:Fas Ligand Protein; D015658:HIV Infections / Q000503:physiopathology; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology; D009369:Neoplasms / Q000503:physiopathology; D010587:Phagocytosis; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction; D019966:Substance-Related Disorders; D014158:Transcription, Genetic; D015854:Up-Regulation; D019014:fas Receptor / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor