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|Title:||Caspase-3 is required for α-fodrin cleavage but dispensable for cleavage of other death substrates in apoptosis|
|Authors:||Jänicke, R.U. |
|Source:||Jänicke, R.U., Ng, P., Sprengart, M.L., Porter, A.G. (1998-06-19). Caspase-3 is required for α-fodrin cleavage but dispensable for cleavage of other death substrates in apoptosis. Journal of Biological Chemistry 273 (25) : 15540-15545. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.273.25.15540|
|Abstract:||Although the commonly activated death protease caspase-3 appears not to be essential for apoptosis during development except in the brain, it was not shown whether substrates known to be cleaved by caspase-3 are still proteolyzed in its absence. We have addressed this question with MCF-7 breast carcinoma cells that we recently showed lack caspase-3 owing to the functional deletion of the CASP-3 gene. Tumor necrosis factor- or staurosporine-induced apoptosis of caspase-3-deficient MCF-7 cells resulted in cleavage of the death substrates PARP, Rb, PAK2, DNA-PK(cs), gelsolin, and DFF-45, but not α-fodrin. In contrast, all these substrates including α- fodrin were cleaved in apoptotic HeLa cells expressing caspase-3. Introduction of CASP-3 cDNA, but not CASP-10 cDNA, into MCF-7 cells restored α-fodrin cleavage. In addition, tumor necrosis factor- or staurosporine- induced apoptosis of MCF-7 cells stably expressing pro-caspase-3 also resulted in α-fodrin cleavage. Although the specific caspase inhibitory peptides Z-VAD-fmk and Z-DEVD-fmk prevented apoptosis of MCF-7 cells, we were unable to detect activation of caspases 2 and 7, which are known to be inhibited by Z-DEVD-fmk. Together our results suggest that caspase-3 is essential for cleavage of α-fodrin, but dispensable for the cleavage of PARP, Rb, PAK2, DNA-PK(cs), gelsolin, and DFF-45 and imply that one or more caspases other than caspases 2, 3, and 7 is activated and plays a crucial role in the cleavage of these substrates in MCF-7 cells.|
|Source Title:||Journal of Biological Chemistry|
|Appears in Collections:||Staff Publications|
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