The mitochondrial protein S mac/DIABLO(second mitochondria-derived activator) performs a critical function in apoptosis by eliminating the inhibitory effect of IAPs (inhibitor of apoptosis proteins) on cas pases. The newly synthesized Smac protein c ontains 239 amino acids. Its N-terminal 55 re sidues encode the mitochondrial-targeting se quence and are proteolytically removed in the mature Smac protein. In the intrinsic cell death pathway, the key event leading to the a ctivation of caspases is the release of several pro-apoptotic proteins such as Smac/DIABL O from the intermembrane space of mitochondria into the cytosol. During apoptosis, Smac is released from mitochondria and re-activates the processed initiator and effector caspases by relieving IAP-mediated inhibition.Furthermore, Smac/DIABLO plays an important regulatory role in the sensitization of cancer cells to both immune-and drug-induced apoptosis.