death-inducing signaling complex assembly

Definition

Target type: biologicalprocess

A process of protein complex assembly in which the arrangement and bonding together of the set of components that form the protein complex is mediated by a death domain (DD) interaction, as part of the extrinsic apoptotic signaling pathway. [GOC:amm, GOC:mtg_apoptosis, InterPro:IPR000488]

The death-inducing signaling complex (DISC) is a protein complex that forms at the cytoplasmic face of the death receptor upon binding of a death ligand. This complex is essential for the initiation of the extrinsic apoptotic pathway, a key mechanism of programmed cell death. Here's a detailed description of the process:

1. **Ligand Binding:** The process starts with the binding of a death ligand, such as TNF-alpha, FasL, or TRAIL, to its corresponding death receptor. These receptors, belonging to the TNF receptor superfamily, have an extracellular domain that binds to the ligand and an intracellular domain that interacts with adaptor proteins.

2. **Adaptor Protein Recruitment:** Ligand binding triggers the receptor's aggregation and the recruitment of adaptor proteins. These proteins, such as FADD (Fas-associated protein with death domain) and TRADD (TNF receptor-associated death domain), contain death domains (DD) that mediate protein-protein interactions.

3. **Caspase-8 Recruitment and Activation:** The adaptor proteins, FADD and TRADD, recruit procaspase-8 (inactive form of caspase-8) to the DISC. The proximity of procaspase-8 molecules within the DISC allows them to autoactivate through a proteolytic cleavage event. This activation of caspase-8 is a crucial step in the apoptotic cascade.

4. **DISC Disassembly and Caspase-8 Activation:** Once caspase-8 is activated, it can cleave other DISC components, including itself, contributing to DISC disassembly. Activated caspase-8 then initiates the apoptotic cascade by activating downstream effector caspases, such as caspase-3 and caspase-7, leading to the execution of cell death.

5. **Alternative DISC Formation:** In some cases, a different DISC can form, known as the "Type II DISC." This DISC involves the recruitment of caspase-10 instead of caspase-8 and typically requires a higher concentration of ligand to form.

6. **Regulation of DISC Formation:** The assembly of the DISC is tightly regulated to prevent inappropriate apoptosis. This regulation involves factors like the expression levels of death receptors and adaptor proteins, the presence of inhibitors, and the interplay of intracellular signaling pathways.'
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Proteins (1)

Compounds (107)