Apoptosis signaling by death receptors

• Published in: European journal of biochemistry Vol. 254; no. 3; pp. 439 - 459
• Main Authors: Schulze‐Osthoff, Klaus, Ferrari, Davide, Los, Marek, Wesselborg, Sebastian, Peter, Marcus E.
• Format: Journal Article
• Language: English
• Published: Berlin & Heidelberg Springer‐Verlag 15-06-1998
• Subjects: activation-induced apoptosis; Animals; APO-1 protein; Apoptosis; Bcl-2; caspase; CD95 (APO‐1/Fas); CD95 antigen; crma-inhibitable protease; death receptor; domain-containing receptor; Fas antigen; fas-mediated apoptosis; Humans; inhibitor of apoptosis protein; interleukin-1-beta converting-enzyme; JNK kinase; nf-kappa-b; nuclear factor-kappa B; nuclear factor‐κB; programmed cell-death; Receptors, Tumor Necrosis Factor - metabolism; Signal Transduction; sphingomyelinase; systemic lupus-erythematosus; TNF-receptor-related apoptosis-mediated protein; TNF-related apoptosis-inducing ligand receptors; tumor-necrosis factor; tumor-necrosis-factor-related apoptosis-inducing ligand tumor-necrosis-factor-receptor-related apoptosis-mediating protein; tumor‐necrosis‐factor‐receptor‐related apoptosis‐mediating protein; tumor‐necrosis‐factor‐related apoptosis‐inducing ligand; zinc-finger protein
• ISSN: 0014-2956; 1432-1033; 1432-1033
• DOI: 10.1046/j.1432-1327.1998.2540439.x

Death receptors have been recently identified as a subgroup of the TNF‐receptor superfamily with a predominant function in induction of apoptosis. The receptors are characterized by an intracellular region, called the death domain, which is required for the transmission of the cytotoxic signal. Currently, five different such death receptors are known including tumor necrosis factor (TNF) receptor‐1, CD95 (Fas/APO‐1), TNF‐receptor‐related apoptosis‐mediated protein (TRAMP) and TNF‐related apoptosis‐inducing ligand (TRAIL) receptor‐1 and ‐2. The signaling pathways by which these receptors induce apoptosis are rather similar. Ligand binding induces receptor oligomerization, followed by the recruitment of an adaptor protein to the death domain through homophilic interaction. The adaptor protein then binds a proximal caspase, thereby connecting receptor signaling to the apoptotic effector machinery. In addition, further pathways have been linked to death receptor‐mediated apoptosis, such as sphingomyelinases, JNK kinases and oxidative stress. These pro‐apoptotic signals are counteracted by several mechanisms which inhibit apoptosis at different levels. This review summarizes the current and rapidly expanding knowledge about the biological functions of death receptors and the mechanisms to trigger or to counteract cell death.