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Summary
Enzymes called caspases are the executioners of programmed cell death. The IAP (inhibitor of apoptosis) proteins suppress apoptosis by blocking caspase activity and this suppression can be relieved by Smac/DIABLO, a mitochondrial protein released into the cytosol in response to apoptotic stimuli. In their Perspective, Fesik and Shi discuss recent structural and biochemical studies that reveal the molecular basis for the inhibition of caspases by IAPs and the relief of IAP inhibition by Smac/DIABLO.