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  • Title: Smac/DIABLO is required for effector caspase activation during apoptosis in human cells.
    Author: Rajalingam K, Oswald M, Gottschalk K, Rudel T.
    Journal: Apoptosis; 2007 Aug; 12(8):1503-10. PubMed ID: 17440818.
    Abstract:
    Mitochondria play a pivotal role during stress-induced apoptosis as several proapoptotic proteins are released to the cytosol to activate caspases. Smac/DIABLO is one of the proapoptotic proteins released from the mitochondria and has been shown to inactivate IAPs. However, gene knockout studies in mice revealed a redundant role for Smac during development and cell death. By applying RNA interference-mediated loss of function approach, we demonstrate that Smac/DIABLO is required for the activation of effector but not initiator caspases during stress and receptor-mediated cell death in HeLa cells. Cells with reduced Smac resist apoptosis and retained clonogenicity. Our results suggest an obligatory role for Smac/DIABLO in these tumor cells during several pathways of apoptosis induction.
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