title: Molecular mechanisms of death-receptor-mediated apoptosis.
abstract: Apoptosis, also called "programmed cell death", can be induced by a variety of stimuli including activation of death receptors by the corresponding death ligands. Death receptors are a subgroup of the tumor necrosis factor (TNF)/nerve growth factor (NGF) receptor superfamily and are characterized by a death domain, which is required for signal transduction. Upon apoptosis induction, caspases, a family of aspartyl-specific cysteine proteases, are activated, which are the main executioners of apoptosis. Finally, specific death substrates are cleaved, resulting in the morphologic features of apoptosis. Depending on the cell type, activation of mitochondria is of central significance for apoptosis induction. This signaling pathway can be modulated by different pro- and anti-apoptotic proteins such as Bax and Bcl-2, which are localized at the mitochondria. Furthermore, apoptosis initiation can be prevented at the death receptor level by FLICE (caspase-8)-inhibitory proteins (FLIPs). Deregulation of apoptosis is associated with diseases like cancer, autoimmunity, and AIDS. Therefore, the elucidation of cell death pathways and the identification of modulators of apoptosis have many therapeutic implications.
authors.affiliation: Tumor Immunology Program, Division of Immunogenetics, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Sartorius
authors.forename: I
authors.initials: I
authors.lastname: Schmitz
authors.forename: P H
authors.initials: PH
authors.lastname: Krammer
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D008024:Ligands; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D019014:fas Receptor / Q000276:immunology
chemical_list: D008024:Ligands; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor