Modulation of cell death by Bcl-x L through caspase interaction
- 20 January 1998
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 95 (2), 554-559
- https://doi.org/10.1073/pnas.95.2.554
Abstract
The caspases are cysteine proteases that have been implicated in the execution of programmed cell death in organisms ranging from nematodes to humans. Many members of the Bcl-2 family, including Bcl-xL, are potent inhibitors of programmed cell death and inhibit activation of caspases in cells. Here, we report a direct interaction between caspases and Bcl-xL. The loop domain of Bcl-xL is cleaved by caspases in vitro and in cells induced to undergo apoptotic death after Sindbis virus infection or interleukin 3 withdrawal. Mutation of the caspase cleavage site in Bcl-xL in conjunction with a mutation in the BH1 homology domain impairs the death-inhibitory activity of Bcl-xL, suggesting that interaction of Bcl-xL with caspases may be an important mechanism of inhibiting cell death. However, once Bcl-xL is cleaved, the C-terminal fragment of Bcl-xL potently induces apoptosis. Taken together, these findings indicate that the recognition/cleavage site of Bcl-xL may facilitate protection against cell death by acting at the level of caspase activation and that cleavage of Bcl-xL during the execution phase of cell death converts Bcl-xL from a protective to a lethal protein.Keywords
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