[HTML][HTML] Smac, a mitochondrial protein that promotes cytochrome c–dependent caspase activation by eliminating IAP inhibition

C Du, M Fang, Y Li, L Li, X Wang - Cell, 2000 - cell.com
C Du, M Fang, Y Li, L Li, X Wang
Cell, 2000cell.com
We report here the identification of a novel protein, Smac, which promotes caspase
activation in the cytochrome c/Apaf-1/caspase-9 pathway. Smac promotes caspase-9
activation by binding to i nhibitor of a poptosis p roteins, IAPs, and removing their inhibitory
activity. Smac is normally a mitochondrial protein but is released into the cytosol when cells
undergo apoptosis. Mitochondrial import and cleavage of its signal peptide are required for
Smac to gain its apoptotic activity. Overexpression of Smac increases cells' sensitivity to …
Abstract
We report here the identification of a novel protein, Smac, which promotes caspase activation in the cytochrome c/Apaf-1/caspase-9 pathway. Smac promotes caspase-9 activation by binding to i nhibitor of a poptosis p roteins, IAPs, and removing their inhibitory activity. Smac is normally a mitochondrial protein but is released into the cytosol when cells undergo apoptosis. Mitochondrial import and cleavage of its signal peptide are required for Smac to gain its apoptotic activity. Overexpression of Smac increases cells' sensitivity to apoptotic stimuli. Smac is the second mitochondrial protein, along with cytochrome c, that promotes apoptosis by activating caspases.
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