Apoptosis

Anti-apoptotic BCL2 protein

Anti-apoptotic BCL2 protein

Inhibits the oligomerisation effector proteins Bak and Bax on the outer mitochondrial membrane to prevent apoptosis

IAP

Intracellular protein inhibitors of apoptosis

Apaf1

Adaptor protein that oligomerize into a wheel-like heptamer called the apoptosome when associated with cytochrome c. They then recruit initiator caspase-9 proteins which activate downstream executioner caspases in the cascade that induces apoptosis. Bridge between caspases and a pro-apoptotic input signal

Apoptosis

Form of cell death that leads to fragmentation of the DNA, shrinkage of the cytoplasm, membrane changes and cell death, without lysis or damage to neighbouring cells.

Apoptosome

Wheel-like heptamer called the apoptosome protein complex involving Apaf-1 and cytochrome c. Apaf1s in the complex then recruit initiator caspase-9 proteins (activated through an apoptosome-induced conformational change) which activate downstream executioner caspases in the cascade that induces apoptosis.

Bak

Pro-apoptotic regulator protein that oligomerizes into a pore in the outer mitochondrial membrane, upon an intrinsic apoptosis signal, allowing cytochrome-c to enter the cytosol

Bax

Pro-apoptotic regulator protein that oligomerizes into a pore in the outer mitochondrial membrane, upon an intrinsic apoptosis signal, allowing cytochrome-c to enter the cytosol

Survival factor

Bind to cell-surface receptors, activating intracellular signalling pathways that suppress apoptosis (usually by stimulating the synthesis of anti-apoptotic Bcl2 proteins)

Bcl-XL

Binds bax - preventing active bax-bax dimers from forming

BH123 proteins

Pro-apoptotic Bax and Bak proteins

BH3-only proteins

Proteins that induce apoptotic conversion of BH123 into oligomers as a response to apoptosis stimuli

Caspase

Protease that has a cysteine at its active site and cleaves its target proteins at specific aspartic acids.

Caspase classification

Can be divided according to: pro-apoptotic or pro-inflammatory (over simplified classification — also regulate other processes that do not fall in either category)
Can be divided according to position in apoptotic signalling cascade (also corresponds to length of prodomain): Initiators vs Effectors

Pro-apoptotic caspases

Caspase-2, -3, -6, -7, -8, -9, -10

Caspase synthesis

Caspases are synthesized as inactive zymogens containing a prodomain, a p20 large subunit (catalytic domain that consists of the active site) and a p10 small subunit. The zymogens are activated by proteolytic cleavages separates the large and small subunits and removes the prodomain.

Cytochrome c

Soluble home protein that is localized in the mitochondrial inter-membrane space

Death-inducing signalling complex (DISC)

Complex formed when death domain (DD) of activated Fas recruits the adapter protein FADD. FADD in turn, via its death effector domain (DED), recruits and activates Caspase-8.
Extrinsic pathway of apoptosis

Death receptor

Transmembrane protein that functions as cell surface sensors to detect extracellular danger signals by ligand binding — can trigger apoptosis

Executioner procaspase

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

Procaspase substrates

Structure proteins, regulators of transcription/translation, kinases and secondary messengers in signalling pathways

Extrinsic pathway

Apoptosis program that is triggered by the binding of an extracellular signal protein to a death receptor

Fas

A death receptor that triggers apoptosis when bound by an extracellular signal protein

Fas ligand

Transmembrane protein in killer lymphocytes whose expression is induced upon lymphocyte activation -- acts as an extracellular signal that triggers the extrinsic pathway of apoptosis

IAP (inhibitor of apoptosis)

Extracellular signal molecule that inhibits apoptosis.

Initiator procaspase

Caspase-1, -2, -4, -5, -8, -9, -10, -11, -12
Apoptotic caspases that begin the apoptotic process, activating the executioner caspases
Have long prodomains that contain protein motifs: the death effector domain (DED) or the caspase recruitment domain (CARD)

Initiators (upstream), executioners (downstream)

This upstream and downstream relationship is not absolute and may only exist transiently during very early phases of apoptosis.

Intrinsic pathway

Apoptosis program triggered by intracellular signals that cause release into the cytosol of proteins from the mitochondrial intermembrane space

Procaspase

Inactive form of caspase (before proteolytic events)

Programmed cell death

A form of cell death in which a cell kills itself by activating an intracellular death program

p53

A transcription regulatory protein that is activated by damage to DNA and is involved in blocking further progression through the cell cycle

Adaptor proteins

Bridge between caspases and a pro-apoptotic input signal
Worms: ced4
Humans: Apaf1, FADD