HUMAN IAP-LIKE PROTEIN REGULATES PROGRAMMED CELL-DEATH DOWNSTREAM OF BCL-X(L) AND CYTOCHROME-C

The gene encoding human IAP-like protein (hILP) is one of several mamm alian genes with sequence homology to the baculovirus inhibitor of-apo ptosis protein (lap) genes. Here we show that hILP can block apoptosis induced by a variety of extracellular stimuli, including UV light, ch emotoxic drugs, and activation of the tumor necrosis factor and Fas re ceptors. hILP also protected against cell death induced by members of the caspase family, cysteine proteases which are thought to be the pri ncipal effecters of apoptosis. hILP and Bcl-x(L) were compared for the ir ability to affect several steps in the apoptotic pathway. Redistrib ution of cytochrome c from mitochondria, an early event in apoptosis, was not blocked by overexpression of hILP but was inhibited by Bcl-x(L ). In contrast, hILP, but not Bcl-x(L), inhibited apoptosis induced by microinjection of cytochrome c. These data suggest that while Bcl-x(L ) may control mitochondrial integrity, hILP can function downstream of mitochondrial events to inhibit apoptosis.