Please use this identifier to cite or link to this item:
https://doi.org/10.1074/jbc.273.25.15540
Title: | Caspase-3 is required for α-fodrin cleavage but dispensable for cleavage of other death substrates in apoptosis | Authors: | Jänicke, R.U. Ng, P. Sprengart, M.L. Porter, A.G. |
Issue Date: | 19-Jun-1998 | Citation: | 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 | URI: | http://scholarbank.nus.edu.sg/handle/10635/111807 | ISSN: | 00219258 | DOI: | 10.1074/jbc.273.25.15540 |
Appears in Collections: | Staff Publications |
Show full item record
Files in This Item:
There are no files associated with this item.
SCOPUSTM
Citations
444
checked on Jan 31, 2023
WEB OF SCIENCETM
Citations
431
checked on Jan 31, 2023
Page view(s)
228
checked on Feb 2, 2023
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.