CrmA, a poxvirus gene product with a serpin-like structure, blocks a variety of apoptotic death events in cultured cells. Based on the ability of CrmA to inhibit the interleukin-1β converting enzyme in vitro, it has been speculated that interleukin-1β converting enzyme-related proteases (caspases) essential for apoptosis are the cellular targets of CrmA. Here we found that rabbit-pox virus CrmA/SPI-2 inhibits the cleavage of lamin A mediated by a caspase in our cell-free system of apoptosis. In the presence of CrmA/SPI-2 nuclear apoptosis in vitro was blocked at an intermediate stage after collapse of the chromatin against the nuclear periphery and before nuclear shrinkage and disintegration into apoptotic body-like fragments. Using N-(acetyltyrosinylvalinyl-N(ε)-biotinyllysyl) aspartic acid [(2,6- dimethylbenzoyl)-oxy] methyl ketone, which derivatizes the active forms of caspases, we could show that one of five caspases active in the extracts is inhibited both by CrmA/SPI-2 and by a peptide spanning the lamin A apoptotic cleavage site. These results reveal that CrmA/SPI-2 can inhibit a caspase responsible both for lamin A cleavage and for the nuclear disintegration characteristic of apoptosis.
CITATION STYLE
Takahashi, A., Musy, P. Y., Martins, L. M., Poirier, G. G., Moyer, R. W., & Earnshaw, W. C. (1996). CrmA/SPI-2 inhibition of an endogenous ICE-related protease responsible for lamin a cleavage and apoptotic nuclear fragmentation. Journal of Biological Chemistry, 271(51), 32487–32490. https://doi.org/10.1074/jbc.271.51.32487
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