THE BACULOVIRUS P35 PROTEIN INHIBITS FAS-INDUCED AND TUMOR NECROSIS FACTOR-INDUCED APOPTOSIS

The baculovirus p35 gene product inhibits virally induced apoptosis, d evelopmental cell death in Caenorhabditis elegans and Drosophila, and neuronal cell death in mammalian systems. Therefore, p35 likely inhibi ts a component of the death machinery that is both ubiquitous and high ly conserved in evolution. We now show for the first time that p35 als o inhibits Fas- and tumor necrosis factor (TNF)-induced apoptosis. Add itionally, p35 blocks TNF- and Fas-induced proteolytic cleavage of the death substrate poly(ADP-ribose) polymerase from its native 116-kDa f orm to the characteristic 85-kDa form. This cleavage is thought to be catalyzed by an aspartate-specific protease of the interleukin 1 beta- converting enzyme family designated prICE (Lazebnik, Y. A., Kaufmann, S. H., Desnoyers, S., Poirier, G. G., and Earnshaw, W. C. (1994) Natur e 371, 346-347), Our data suggest that p35 must directly or indirectly inhibit prICE. Given that p35 inhibits both TNF and Fas killing, alon g with previous reports of its ability to block developmental, viral, and x-irradiation-induced cell death, the present results indicate tha t TNF- and Fas-mediated apoptotic pathways must have components in com mon with these highly conserved death programs.