Apoptosomes: engines for caspase activation.
Activation of the caspases that initiate apoptosis typically requires cognate scaffold proteins, including CED-4 in Caenorhabditis elegans, Apaf-1 in mammals and Dark in Drosophila. Each scaffold protein oligomerizes procaspases into a complex called the apoptosome, but the regulation and biological roles of the scaffolds differ. Whereas CED-4 is restrained by the Bcl-2 homologue CED-9, Apaf-1 is inhibited by its WD40 repeat region, until it is activated by cytochrome c, derived from damaged mitochondria. Although Dark also has a WD40 region, its activation does not seem to involve cytochrome c. CED-4 is essential for apoptosis in the worm and Dark for many apoptotic responses in the fly, but the Apaf-1/caspase-9 system probably amplifies rather than initiates the mammalian caspase cascade.
Adams
Jerry M
JM
The Walter and Eliza Hall Institute of Medical Research, Melbourne, 3050, Victoria, Australia. adams@wehi.edu.au
Cory
Suzanne
S
D000818:Animals; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000502:physiology; D020169:Caspases / Q000378:metabolism*; D029721:Drosophila Proteins; D004789:Enzyme Activation; D046911:Macromolecular Substances; D008954:Models, Biological; D009369:Neoplasms / Q000209:etiology; D011506:Proteins / Q000737:chemistry / Q000502:physiology; D015398:Signal Transduction
D053477:Apoptotic Protease-Activating Factor 1; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; C089224:Ced-4 protein, C elegans; D029721:Drosophila Proteins; D046911:Macromolecular Substances; D011506:Proteins; C400550:dark protein, Drosophila; D020169:Caspases