regulation of extrinsic apoptotic signaling pathway via death domain receptors

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of extrinsic apoptotic signaling pathway via death domain receptors. [GOC:TermGenie, PMID:17245429]

The extrinsic apoptotic signaling pathway, also known as the death receptor pathway, is initiated by the engagement of death receptors on the cell surface by their cognate ligands. These receptors are members of the TNF receptor (TNFR) superfamily and share a conserved cytoplasmic domain known as the death domain. Upon ligand binding, death receptors trimerize and recruit adaptor proteins, such as Fas-associated protein with death domain (FADD) and TNF receptor-associated death domain (TRADD), through their death domains. These adaptor proteins further recruit procaspase-8 (or procaspase-10) to the death-inducing signaling complex (DISC), a multiprotein complex that forms at the cytoplasmic tail of the death receptor. Procaspase-8, a key initiator caspase, is then activated through proteolytic cleavage within the DISC, leading to a cascade of caspase activation.

Active caspase-8 can directly cleave effector caspases (caspase-3, caspase-6, and caspase-7), which execute the apoptotic program. In some cell types, caspase-8 activates Bid, a BH3-only protein that can amplify the apoptotic signal by inducing the mitochondrial pathway.

The extrinsic apoptotic signaling pathway plays a crucial role in various physiological processes, including immune homeostasis, development, and elimination of damaged cells. It is tightly regulated to prevent inappropriate activation and maintain cellular integrity.

Several mechanisms are involved in regulating this pathway:

* **Ligand availability**: The expression and release of death ligands are tightly controlled.
* **Receptor expression**: The levels of death receptors on the cell surface can be modulated.
* **Inhibitory proteins**: Proteins such as FLIP (FLICE-inhibitory protein) can bind to caspase-8 and prevent its activation.
* **Cellular signaling pathways**: Various intracellular signaling pathways, including NF-κB and PI3K/Akt, can modulate the activity of death receptors.

Dysregulation of the extrinsic apoptotic signaling pathway can lead to various pathological conditions, such as autoimmune diseases, cancer, and neurodegenerative disorders.'
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Proteins (1)

Compounds (9)