Smac/DIABLO is required for effector caspase activation during apoptosis in human cells |
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Authors: | Krishnaraj Rajalingam Monique Oswald Kathleen Gottschalk Thomas Rudel |
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Institution: | (1) Department of Molecular Biology, Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany;(2) Present address: Institut fur Medizinische Strahlenkunde und Zellforschung, Bayerische Julius-Maximilians-Universitat, Versbacher-Str. 5, 97078 Wurzburg, Germany |
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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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Keywords: | Apaf-1 Caspase Smac/DIABLO ER-stress Apoptosis |
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