Anti-apoptotic potential of insect cellular and viral IAPs in mammalian cells.
IAPs were identified as baculoviral proteins that could inhibit the apoptotic response of insect cells to infection. Of the viral IAPs, OpIAP and CpIAP can inhibit apoptosis, whereas AcIAP cannot. OpIAP and some mammalian homologues can inhibit mammalian cell death. Two mammalian IAPs bind to TNFRII associated factors (TRAFs), but the significance of this is unclear. Here we show that Drosophila cellular IAPs and two baculoviral IAPs (OpIAP and CpIAP) can inhibit mammalian cell death induced by overexpression of Caspases 1 and 2. IAPs must act on conserved components of the apoptotic mechanism, but as none of these IAPs could bind TRAF proteins, TRAFs are not likely to be important for IAP mediated apoptosis inhibition. As OpIAP protected against death induced by ligation of TNF receptor family members, but not by factor nor serum withdrawal from dependent cells, it can inhibit certain apoptotic pathways without affecting others.
Hawkins
C J
CJ
The Walter and Eliza Hall Institute for Medical Research, Post Office Royal Melbourne Hospital, Victoria, 3050, Australia.
Ekert
P G
PG
Uren
A G
AG
Holmgreen
S P
SP
Vaux
D L
DL
D000818:Animals; D017209:Apoptosis; D004330:Drosophila; D029721:Drosophila Proteins; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D007313:Insecta; D008322:Mammals; D016716:PC12 Cells; D011506:Proteins / Q000378:metabolism; D051381:Rats; D047992:TNF Receptor-Associated Factor 2; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
C111892:DIAP2 protein, Drosophila; D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D011506:Proteins; D047992:TNF Receptor-Associated Factor 2; D014764:Viral Proteins; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus