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Smac/DIABLO is required for effector caspase activation during apoptosis in human cells
Authors:Krishnaraj Rajalingam  Monique Oswald  Kathleen Gottschalk  Thomas Rudel
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
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.
Keywords:Apaf-1  Caspase  Smac/DIABLO  ER-stress  Apoptosis
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