Activation of caspases triggered by cytochrome c in vitro

Previous studies hare shown that Apaf-1 and caspase-9 in the presence of cytochrome c and dATP can form an initiating complex for an apoptotic protease cascade. We have developed a cytochrome c-dependent in vitro system in which caspases downstream of this initiation complex are activated. The activation of caspase-9 from zymogen form to active dimeric protease requires intrinsic enzymatic activity, In contrast, caspase-3 and caspase-7 zymogens are proteolytically processed by active caspase-9, Activation of the above caspases is blocked by a dominant negative form of caspase-9, The in vitro system displays surprising specificity in that other caspases, including 1, 2, 4, 8, 10, and 13, are not activated. (C) 1998 Federation of European Biochemical Societies.