CrmA/SPI-2 Inhibition of an Endogenous ICE-related Protease Responsible for Lamin A Cleavage and Apoptotic Nuclear Fragmentation

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作者：

A Takahashi，PY Musy，LM Martins，GG Poirier，RW Moyer，WC Earnshaw

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摘要：

CrmA, a poxvirus gene product with a serpin-like structure, blocks a variety of apoptotic events in cultured cells. Based on the ability of CrmA to inhibit the in vitro, it has been speculated that -related (caspases) essential for are the cellular targets of CrmA. Here we found that CrmA/inhibits the cleavage of mediated by a caspase in our cell-free system of . In the presence of CrmA/, nuclear in vitro was blocked at an intermediate stage after collapse of the against the nuclear periphery and before nuclear shrinkage and disintegration into apoptotic body-like fragments. Using N-(acetyltyrosinylvalinyl-Nepsilon-biotinyllysyl) aspartic acid [(2,6-dimethylbenzoyl)oxy] , which derivatizes the active forms of caspases, we could show that one of five caspases active in the extracts is inhibited both by CrmA/and by a spanning the apoptotic cleavage site. These results reveal that CrmA/can inhibit a caspase responsible both for cleavage and for the nuclear disintegration characteristic of .

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关键词：

Animals Cell-Free System Poxviridae Poly(ADP-ribose) Polymerases Endopeptidases Cysteine Endopeptidases Serpins Viral Proteins Nuclear Proteins Lamins