Module 12- Apoptosis

A form of programed cell death in which a "suicide" program is activated within an animal cell. This leads to rapid cell death mediated by intracellular proteolytic enzymes called caspases.

Apoptosis

A form of programmed cell death in which the damaged cell bursts, releasing intracellular molecules into the extracellular space, potentially triggering immune or inflammatory responses.

Cell necrosis

A family of signal protein receptors containing eight members, including Fas and TNF. These proteins contain an extracellular ligand-binding domain, a single transmembrane domain, and an intracellular death domain required to activate the extrinsic pathway of apoptosis.

TNF (tumor necrosis factor) family of signal proteins

Intracellular proteases that are involved in mediating the intracellular events of apoptosis.

Caspases

Pathway of apoptosis triggered by cell injury, DNA damage, a lack of oxygen, a lack of extracellular survival factors, or in response to intracellular developmental signals. Also known as the mitochondrial pathway of apoptosis.

Intrinsic pathway of apoptosis

A trimeric ligand that activates its trimeric cell-surface death receptor triggering the extrinsic pathway of apoptosis. This transmembrane protein is expressed on multiple cell types such as killer (cytotoxic) lymphocytes.

Fas ligand

Receptors that bind extracellular death ligands, but lack the intracellular death domains necessary for the binding of an adaptor protein and activation of the amplifying proteolytic cascade.

Decoy receptors

Apoptotic caspases that begin the apoptotic process, activating the executioner caspases.

Initiator caspases

A main effector Bcl2 family protein of the intrinsic pathway of apoptosis that is bound to the mitochondrial outer membrane even in the absence of an apoptotic signal. Is usually activated by pro-apoptotic BH3-only proteins.

Bak

A mammalian inhibitor of apoptosis protein that is encoded on the X chromosome and located in the cytosol. It binds to and inhibits initiator caspase-9 as well as executioner caspase-3 and caspase-7. This protein sets an inhibitory threshold these caspases must overcome to trigger apoptosis.

XIAP

A negatively charged phospholipid that is normally confined to the cytoplasmic leaflet of the lipid bilayer of the plasma membrane. In apoptotic cells, it accumulates in the outer leaflet, where it serves as an "eat me" signal to the neighboring phagocytic cells.

Phosphatidylserine

Complex in which initiator caspases interact and are activated after extracellular ligands bind to cell-surface death receptors in the extrinsic pathway of apoptosis.

DISC (death-inducing signaling complex)

A main effector Bcl2 family protein of the intrinsic pathway of apoptosis that is located mainly in the cytosol. It translocates to the mitochondria only after activation, usually by activated pro-apoptotic BH3-only proteins.

Bax

Transmembrane receptor proteins that can signal the cell to undergo apoptosis when it binds its extracellular ligand.

Death receptors

A serine-threonine kinase that acts in the PI-3-kinase Akt intracellular signaling pathway that is also known as protein kinase B (PKB). This kinase is activated by the binding of a survival factor. The active kinase phosphorylates and inactivates the BH3-only protein Bad.

Akt

A homotypic protein interaction domain found on death receptors that is composed of a bundle of six α-helices and related in sequence and structure to the caspase recruitment domain (CARD). This domain is required for death receptors to activate the extrinsic pathway of apoptosis.

Death domain (DD)

A soluble component of the electron-transport chain. When released into the cytosol from the mitochondrial intermembrane space, it initiates apoptosis.

Cytochrome c

A homotypic protein interaction domain found on Apaf1 that is composed of a bundle of six α-helices and related in sequence and structure to the death domain (DD). When exposed on Apaf1, this domain recruits an inactive caspase-9 monomer.

CARD (caspase recruitment domain)

A homology domain that is found in all members of the Bcl2 family. The Bcl2 family proteins differ in the number of these domains that they contain (BH1, BH2, BH3, BH4).

BH domain (Bcl2 homology)

Trimeric transmembrane death receptors that initiate apoptosis when they bind their extracellular trimeric ligand.

Fas death receptors

An intracellular blocking protein that resembles an initiator caspase, but lacks the protease domain necessary for the activation of the proteolytic cascade. This protein competes with initiator caspases for binding sites on DISC, but since it cannot cleave its partner it is unable to form stable activated initiator caspases.

FLIP

A BH3-only protein that links the extrinsic and intrinsic pathways of apoptosis. When the extrinsic pathway is activated, the initiator caspase-8 cleaves this protein to produce a truncated active version. This active version translocates to the mitochondria and inhibits anti-apoptotic Bcl2 proteins.

Bid

A small intracellular adaptor protein containing death domains that connects Fas receptor to the caspase cascade.

FADD (Fas-associated death domain)

Intracellular protein inhibitors of apoptosis that bind to and inhibit caspases.

IAPs (inhibitors of apoptosis)

The change in the outer mitochondrial membrane that releases cytochrome c and other soluble proteins from the intermembrane space into the cytosol. This is a critical step in the intrinsic pathway of apoptosis.

Mitochondrial outer membrane permeabilization (MOMP)

An adapter protein of the intrinsic apoptotic pathway. When it binds cytochrome c, it oligomerizes to form an apoptosome.

Apaf1 (apoptotic protease activating factor-1)

Pro-apoptotic proteins that contain BH1, BH2, BH3 domains that form aggregates in the mitochondrial outer membrane and trigger the release of cytochrome c and other intermembrane-space proteins.

Effector Bcl2 family proteins

Apoptotic caspases that catalyze the widespread cleavage during apoptosis that kill the cell.

Executioner caspases

Proteins that are produced in response to various apoptotic stimuli and by binding to inhibitory anti-apoptotic proteins, prevent their binding to a caspase. This therefore blocks the inhibition of apoptosis provided by IAPs.

Anti-IAP proteins

A heptamer of Apaf1 proteins that forms upon activation of the intrinsic apoptotic pathway. It recruits and activates initiator caspases that will activate downstream executioner caspases to induce

Apoptosome

Pathway of apoptosis triggered by the binding of extracellular signals to transmembrane death receptors.

Extrinsic pathway of apoptosis

A pro-apoptotic protein BH3-only protein that when unphosphorylated, promotes apoptosis by binding to and inhibiting anti-apoptotic Bcl2. When phosphorylated, this protein releases bound Bcl2.

Bad

Extracellular signal molecules that inhibit apoptosis. They act as social controls to ensure that individual cells survive or die, depending on what is best for the organism as a whole.

Survival factors

An inactive, soluble monomeric version of the initiator caspases found in the cytosol.

Procaspase

Anti-apoptotic family protein of the outer mitochondrial membrane that binds and inhibits pro-apoptotic Bcl2 family proteins. Prevents inappropriate activation of the intrinsic pathway of apoptosis. This protein is the first family member discovered, known as B cell lymphoma-2.

Bcl2

Family of intracellular proteins that either promote or inhibit apoptosis by regulating the release of cytochrome c and other mitochondrial proteins from the intermembrane space into the cytosol.

Bcl2 family

Largest subclass of Bcl2 family proteins that are produced or activated in response to an apoptotic stimulus. These proteins promote apoptosis mainly by inhibiting anti-apoptotic proteins in the Bcl2 family.

BH3-only proteins

Anti-apoptotic Bcl2 family protein of the outer mitochondrial membrane that binds and inhibits pro-apoptotic Bcl2 family proteins. Prevents inappropriate activation of the intrinsic pathway of apoptosis. This protein is known as B cell lymphoma-2 extra-large.

BclxL

Proteins on the cytosolic surface of the outer mitochondrial membrane containing all four BH domains that bind and inhibit pro-apoptotic effector Bcl2 family proteins. They also help prevent inappropriate activation of the intrinsic pathway of apoptosis.

Anti-apoptotic Bcl2 family proteins

Type of programmed cell death in which the damaged cell bursts open, releasing intracellular molecules into the extracellular space, potentially triggering immune or inflammatory responses.

Necrosis