Correspondence to K. Schulze-Osthoff, Department of Internal Medicine I, Medical Clinics, Eberhard-Karls-University, Otfried-Müller-Str. 10, D-72076 Tübingen, Germany
Apoptosis signaling by death receptors
Article first published online: 25 DEC 2001
European Journal of Biochemistry
Volume 254, Issue 3, pages 439–459, June (II) 1998
How to Cite
Schulze-Osthoff, K., Ferrari, D., Los, M., Wesselborg, S. and Peter, M. E. (1998), Apoptosis signaling by death receptors. European Journal of Biochemistry, 254: 439–459. doi: 10.1046/j.1432-1327.1998.2540439.x
Fax: +49 7071 29 5865.
Abbreviations. AICD, activation-induced cell death; Apaf, apoptotic protease-activating factor; CAD, caspase-activated DNase; CARD, caspase recruitment domain; CD95L, CD95 ligand; CrmA, cytokine response modifier A; DcR, decoy receptor; DD, death domain; DED, death effector domain; DR, death receptor; DISC, death-inducing signaling complex; FADD, Fas-associated death domain protein; FAN, factor-associated neutral sphingomyelinase; FAP; Fas-associated phosphatase; FLICE, FADD-like ICE; FLIP, FLICE-inhibitory protein; IAP, inhibitor of apoptosis protein; ICE, interleukin-1β-converting enzyme; JNK, c-Jun N-terminal kinase; LT, lymphotoxin; MADD, mitogen-activated kinase activating death domain protein; MAP, mitogen-activated protein; mTNF, membrane-bound TNF; NF-κB, nuclear factor-kappa B; PAK, p21-activated kinase; PARP, poly(ADP-ribose) polymerase; RAIDD, RIP-associated ICH-1/Ced-3 homologous death domain protein; RIP, receptor-interacting protein; SAPK, stress-activated protein kinase; SMase, sphingomyelinase; sTNF, soluble TNF; TNF, tumor necrosis factor; TNF-R, TNF receptor; TRADD, TNF receptor-associated death domain protein; TRAF, TNF receptor-associated factor; TRAIL, TNF-related apoptosis-inducing ligand; TRAMP, TNF receptor-related apoptosis-mediating protein.
Note. This Review will be reprinted in EJB Reviews 1998 which will be available in April 1999.
- Issue published online: 25 DEC 2001
- Article first published online: 25 DEC 2001
- (Received 16 February/25 March 1998)
- Cited By
- CD95 (APO-1/Fas);
- death receptor;
- inhibitor of apoptosis protein;
- nuclear factor-κB;
- tumor-necrosis factor;
- tumor-necrosis-factor-related apoptosis-inducing ligand;
- tumor-necrosis-factor-receptor-related apoptosis-mediating protein.
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.