death receptor activity

Definition

Target type: molecularfunction

Combining with an extracellular messenger (called a death ligand), and transmitting the signal from one side of the plasma membrane to the other to initiate apoptotic or necrotic cell death. [GOC:bf, GOC:BHF, GOC:ecd, GOC:mtg_apoptosis, GOC:rl, PMID:10209153]

Death receptor activity is a fundamental process in apoptosis, a form of programmed cell death essential for maintaining tissue homeostasis and eliminating damaged or unwanted cells. It involves the activation of transmembrane proteins, known as death receptors, upon binding to their specific ligands, primarily tumor necrosis factor (TNF) family members. This binding triggers a cascade of intracellular signaling events, ultimately leading to the activation of caspases, a family of cysteine proteases responsible for dismantling cellular components.

Death receptor signaling pathways are highly regulated, involving multiple molecular interactions and checkpoints to ensure precise and controlled cell death. Upon ligand binding, death receptors undergo conformational changes, exposing their death domain, which recruits adaptor proteins like TRADD (TNF receptor-associated death domain) and FADD (Fas-associated death domain). These adaptors, in turn, bind to procaspase-8, a proenzyme precursor of caspase-8, leading to its activation. Activated caspase-8 initiates a cascade of caspase activation, eventually culminating in the activation of executioner caspases, such as caspase-3, which cleave cellular substrates and dismantle the cell.

Death receptor activity is crucial for a wide range of physiological processes, including immune regulation, development, and elimination of harmful cells. It is also implicated in various pathological conditions, including cancer, autoimmune diseases, and neurodegenerative disorders. Dysregulation of death receptor signaling can contribute to uncontrolled cell survival or excessive apoptosis, contributing to disease progression. Understanding the molecular mechanisms of death receptor activity is essential for developing targeted therapies for a range of diseases.'
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Proteins (1)

Compounds (3)