Human IAP-like protein regulates programmed cell death downstream of Bcl-xL and cytochrome c.
The gene encoding human IAP-like protein (hILP) is one of several mammalian genes with sequence homology to the baculovirus inhibitor-of-apoptosis protein (iap) genes. Here we show that hILP can block apoptosis induced by a variety of extracellular stimuli, including UV light, chemotoxic drugs, and activation of the tumor necrosis factor and Fas receptors. hILP also protected against cell death induced by members of the caspase family, cysteine proteases which are thought to be the principal effectors of apoptosis. hILP and Bcl-xL were compared for their ability to affect several steps in the apoptotic pathway. Redistribution of cytochrome c from mitochondria, an early event in apoptosis, was not blocked by overexpression of hILP but was inhibited by Bcl-xL. In contrast, hILP, but not Bcl-xL, inhibited apoptosis induced by microinjection of cytochrome c. These data suggest that while Bcl-xL may control mitochondrial integrity, hILP can function downstream of mitochondrial events to inhibit apoptosis.
Duckett
C S
CS
Howard Hughes Medical Institute, and Department of Medicine, The University of Chicago, Illinois 60637, USA.
Li
F
F
Wang
Y
Y
Tomaselli
K J
KJ
Thompson
C B
CB
Armstrong
R C
RC
D017209:Apoptosis / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D003574:Cytochrome c Group / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins; D005786:Gene Expression Regulation; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D001426:Bacterial Proteins; D003574:Cytochrome c Group; D029968:Escherichia coli Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; C054221:iap protein, E coli