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  • Title: Inhibition of the Caenorhabditis elegans cell-death protease CED-3 by a CED-3 cleavage site in baculovirus p35 protein.
    Author: Xue D, Horvitz HR.
    Journal: Nature; 1995 Sep 21; 377(6546):248-51. PubMed ID: 7675111.
    Abstract:
    The baculovirus protein p35 inhibits programmed cell death in such diverse animals as insects, nematodes and mammals. Here we show that p35 protein is a substrate for and inhibitor of the Caenorhabditis elegans cell-death protease CED-3 (refs 6, 7) and a substrate for four CED-3-like vertebrate cysteine protease activities implicated in apoptosis in mammals. A p35 mutation that greatly reduced p35 activity in vitro as a CED-3 substrate and inhibitor abolished p35 activity in vivo in protecting against cell death in C. elegans. Introduction of the CED-3 cleavage site in p35 into the cowpox virus protein crmA, which inhibits mammalian apoptosis but not programmed cell death in C. elegans, caused crmA to block CED-3-mediated cell death. These observations suggest that p35 may prevent programmed cell death in C. elegans and other species by acting as a competitive inhibitor of cysteine proteases.
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