CrmA/SPI-2 inhibition of an endogenous ICE-related protease responsible for lamin a cleavage and apoptotic nuclear fragmentation

61Citations
Citations of this article
19Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

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.

Cite

CITATION STYLE

APA

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

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free