Death-inducing signalling complex caspase

DISC, death inducing signaling complex DSS, dextran sulfate sodium FLIP, caspase-8 (FLICE) inhibitory protein... 

Extrinsic (death receptor) pathway of caspase activation during apoptosis involves the binding of death ligands to cell surface receptors (e.g., Fas/ CD95/Apo-l or TNF receptor), recruitment of adaptor molecules Fas-associated death domain (FADD) or TNF receptor-associated death domain (TRADD) to the cytosolic end of the receptor, and formation of the death-inducing signaling complex (DISC) at the plasma membrane. DISC recruits and activates the initiator caspases, caspase-8 or -10. 

A similar process occurs for caspase-8 activation. In this case, oligomerization of the death adaptor protein Fas-Associated Death Domain (FADD) recruits procaspase-8 into the death-inducing signalling complex (DISC) allowing caspase-8 dimerization and subsequent activation (Shi, 2006). 

The TRADD or FADD domains bind to adapter proteins in the cytosol and together they form of a death inducing signaling complex (DISC). This complex recruits caspase-8, one of a family of calcium ion-activated serine proteases (caspases) which cleave polypeptides on the C-terminal side of their aspartate residues. DISC activates caspase-8 to activate a Bcl-2 activator, BID (Fig. 13.1 Oa). The resultant tBid fragment activates effector Bcl-2 proteins on the endoplasmic reticular membrane and mitochondrial outer membrane. 

At present, there are two relatively well-characterized cell death pathways that result in the activation of executioner caspases (Figure 2). One is receptor-mediated and the other is mitochondrial-dependent. On receiving an apoptotic stimulus, the receptor-depen-dent pathway is initiated by activation of cell death receptors such as Fas and tumor necrosis factor. The death receptor stimulation results in the formation of a death inducing signaling complex (DISC) that recruits and activates procaspase-8, which in turn cleaves and... 

The Fas receptor (CD95) binds the Fas ligand (FasL), a transmembrane protein part of TNF family. The interaction between Fas and FasL results in the formation of death-inducing signaling complex (DISC), which contains the FADD., caspase-8, and caspase-10. In some types of cells, processed caspase-8 directly activates other members of the caspase family and triggers the execution of apoptosis of the cell. In other types of cells (type II), the Fas-DISC triggers the release of proapoptotic factors from mitochondria and the amplified activation of caspase-8 [24]. 

Won K-J, Chung K-S, Lee YS, Alia MS, Pervez MK, Fatima S, Choi J-H, Lee K-T (2010) Haplophytin-A induces caspase-8-mediated apoptosis via the formation of death-inducing signaling complex in human promyelocytic leukemia HL-60 cells. Chem Biol Interact 188 505-511... 

The large prodomains of procaspases contain structural motifs that belong to the death domain (DD) superfamily involved in the transduction of the apoptotic signals. This superfamily consists of the DD, the death effector domain (DED), and the caspase recruitment domain (CARD). Each of these motifs interacts with other proteins by homotypic interactions. DED is found in procaspase-8 and -10, and CARD is found in procaspase-1, -2, -4, -5, -9, -11, and -12. DED and CARD are responsible for the recruitment of initiator caspases into death- or inflammation-inducing signaling complexes, resulting in proteolytic autoactivation of caspases that subsequently initiates inflammation and apoptosis [26, 29, 30],... 

Harper, N., Hughes, M., MacFarlane, M., and Cohen, G.M. (2003) Fas-associated death domain protein and caspase-8 are not recruited to the tumor necrosis factor receptor 1 signaling complex during tumor necrosis factor-induced apoptosis. J. Biol. Chem., 278 25534-25541. 

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