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Updated: Jul 15, 2026

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
Published on: August 2, 2021
Smac/DIABLO is required for effector caspase activation during apoptosis in human cells
Krishnaraj Rajalingam1, Monique Oswald, Kathleen Gottschalk
1Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117, Berlin, Germany.
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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