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Biochemistry and function of the DISC

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  • Ion channels in the regulation of apoptosis

    2015, Biochimica et Biophysica Acta - Biomembranes
    Citation Excerpt :

    Extracellular pro-apoptotic signals or ligands and their respective receptors include FAS/CD95 ligand—binds to CD95, TNFα—binds to TNFR1, TNF-related apoptosis inducing ligand (TRAIL)—binds to TRAILR1–2, and others [31]. Binding of ligands to death receptors initiates the formation of multiprotein complex dubbed death-inducing signaling complex (DISC), resulting in activation of initiator caspase-8 [32]. Active caspase 8 directly activates caspase-3, thereby triggering caspase-dependent apoptosis.

  • Structural studies of death receptors

    2014, Methods in Enzymology
    Citation Excerpt :

    Binding of the ligand CD95L (FasL and Apo1L) leads to serial recruitment of the immediate adaptor protein Fas-associated with a DD (FADD) and procaspase-8 and -10, two closely related cysteine proteases, and regulatory homologues of the caspase-8/-10 from the cellular FLICE inhibitory protein (cFLIP) family (FLICE: FADD-like interleukin 1β-converting enzyme). The receptor-accreted assembly of proteins is called the death-inducing signaling complex (DISC) (Algeciras-Schimnich et al., 2002; Kischkel et al., 1995; Walczak & Sprick, 2001). Induced proximity of the procaspases within the DISC leads to autoproteolysis and release into the cytosol of active caspase heterotetramers that initiate signaling cascades that can proceed to programmed cell death (Medema et al., 1997).

  • Apoptosis in the anucleate platelet

    2012, Blood Reviews
    Citation Excerpt :

    This serves to recruit and activate the apoptosis-initiating proteases, procaspase-8 and/or procaspase-10, forming a death-inducing signaling complex (DISC) assembled on the cytoplasmic side of the plasma membrane. Activated caspases 8 and/or 10, in turn, activate the executioner (effector) caspases 3, 6 and 7 that cleave vital cell proteins and shift the apoptotic process to the execution phase, the point of no return.47,94–103 Some members of the TNFR superfamily, called decoy receptors (DcR), do not contain cytoplasmic death domains (Table 2).

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