Ch 18: Cell Death

Flashcards about Cell Death

p53

A protein that functions to prevent tumor formation by inducing programmed cell death or halting the cell cycle when DNA is damaged. This protein is frequently inactivated or mutated in approximately half of human cancers, highlighting its crucial role in maintaining genomic stability.

BH3-mimetic drugs

A class of synthetic molecules designed to disrupt the activity of anti-apoptotic Bcl2 family proteins. They achieve this by occupying the BH3-binding groove, which is essential for protein-protein interactions that suppress programmed cell death, thereby liberating the intrinsic pathway of apoptosis.

Carcinomas

The most prevalent type of cancer in humans, originating from epithelial tissues that line organs and cavities, such as those found in the lungs, intestines, mammary glands, and prostate gland.

Apoptosis

A regulated process of cellular self-destruction characterized by cell shrinkage, chromatin condensation, and DNA fragmentation. The dying cell is then consumed by phagocytes. This process is orchestrated by a family of proteases known as caspases.

Caspases

A family of cysteine-aspartic proteases that execute programmed cell death by cleaving over a hundred of intracellular substrates after specific aspartic acid residues, disassembling the cells from within.

Initiator Caspases

A group of the proteases that, upon activation, initiate the caspase cascade in programmed cell death. Their activation is typically triggered by adaptor proteins in response to stimuli, causing them to dimerize and become catalytically active.

Executioner Caspases

A group of the proteases that, once activated by their initiator counterparts, dismantle the cell by cleaving numerous structural and regulatory proteins.

Extrinsic Pathway

A pathway of programmed cell death activated by the binding of extracellular ligands to death receptors on the cell surface. An example involves Fas ligand binding to its receptor.

Intrinsic Pathway

A pathway of programmed cell death initiated by intracellular signals, such as stress or developmental cues, that converge on the mitochondria, leading to the permeabilization of its outer membrane.

MOMP

The permeabilization of the outer mitochondrial membrane, resulting in the release of proteins, such as cytochrome c, from the intermembrane space into the cytosol, initiating the intrinsic pathway of controlled cell death.

Apoptosome

A multimeric protein complex formed during the intrinsic pathway. It activates caspase-9, which in turn activates other caspases, leading to cell death.

BH3-binding groove

A structural feature of pro-survival Bcl2 family proteins that binds pro-apoptotic BH3-only proteins, thereby preventing the former from inhibiting programmed cell death.

venetoclax

A specific type of BH3-mimetic drug that selectively binds to the BH3-binding groove of Bcl2, displacing pro-apoptotic proteins and inducing programmed cell death in cells that rely on Bcl2 for survival.

Fas Ligand

A protein displayed on the plasma membrane of killer lymphocytes that interacts with Fas, a death receptor, found on the surface of target cells, thereby activating a cascade of caspases that leads to the demise of the target cell.

Apaf1

A protein activated by cytochrome c in the cytoplasm, which leads to the activation of caspases and subsequent apoptosis.