Caspase-2- induced Apoptosis Requires Bid Cleavage: A Physiological Role for Bid in Heat Shock-induced Death.
The mechanisms through which Caspase-2 leads to cell death are controversial. Here we show, using a combination of cell-free and cell culture-based approaches, that cleavage of the Bcl-2-family protein Bid is required for the induction of apoptosis by Caspase-2. Caspase-2 promoted cytochrome c release from mitochondria in the presence of cytosol from wild-type, but not Bid-deficient, mouse embryonic fibroblasts (MEFs). Recombinant wild-type Bid, but not a noncleavable mutant (D59E), restored cytochrome c release. Similarly, Bid-null MEFs were relatively resistant to apoptosis triggered by active Caspase-2, and apoptosis was restored in Bid-null cells by the expression of wild-type, but not D59E, Bid. Finally, Bid-null MEFs were substantially more resistant to apoptosis induced by heat shock, which has been shown to be dependent on apical activation of Caspase-2. The data are consistent with a model in which Caspase-2 induces apoptosis via cleavage of Bid at D59 and the subsequent engagement of the mitochondrial (intrinsic) pathway.[1]References
- Caspase-2-induced Apoptosis Requires Bid Cleavage: A Physiological Role for Bid in Heat Shock-induced Death. Bonzon, C., Bouchier-Hayes, L., Pagliari, L.J., Green, D.R., Newmeyer, D.D. Mol. Biol. Cell (2006) [Pubmed]
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