The baculovirus anti-apoptotic protein Op-IAP does not inhibit Drosophila caspases or apoptosis in Drosophila S2 cells and instead sensitizes S2 cells to virus-induced apoptosis.
The Op-IAP protein from the baculovirus Orgyia pseudotsugata M nucleopolyhedrovirus (OpMNPV) is highly effective at inhibiting apoptosis triggered by a variety of different stimuli in lepidopteran cells as well as in several different mammalian cell types, suggesting that it functions at a highly conserved step in the apoptotic pathway. However, the mechanism by which Op-IAP inhibits apoptosis is unclear. Since some IAP proteins can bind and inhibit caspases, we tested whether Op-IAP could inhibit the activity of caspases from Drosophila melanogaster. We found that recombinant Op-IAP protein was not able to bind or directly inhibit the activity of the Drosophila caspases DRONC, DrICE, or DCP-1 in vitro. In addition, expression of Op-IAP was unable to inhibit apoptosis triggered by either actinomycin D or UV light in D. melanogaster S2 cells. Surprisingly, Op-IAP expression in S2 cells enhanced apoptosis caused by baculovirus infection, but did not cause increased sensitivity to either actinomycin D or UV damage-induced apoptosis. The observation that Op-IAP cannot inhibit these insect caspases suggests that it functions by a mechanism that does not involve direct caspase inhibition.
Wright
Casey W
CW
Molecular, Cellular and Developmental Biology Program, Division of Biology, Kansas State University, 232 Ackert Hall, Manhattan, KS 66506, USA.
Means
John C
JC
Penabaz
Taryn
T
Clem
Rollie J
RJ
D000818:Animals; D017209:Apoptosis; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004331:Drosophila melanogaster / Q000201:enzymology*; D051034:Inhibitor of Apoptosis Proteins; D009036:Moths / Q000821:virology*; D017924:Nucleopolyhedroviruses / Q000378:metabolism / Q000472:pathogenicity*; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D018411:Spodoptera / Q000821:virology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology
D061945:Caspase Inhibitors; D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D011506:Proteins; D014764:Viral Proteins; D020169:Caspases; C103568:Dcp-1 protein, Drosophila; C109171:drICE protein, Drosophila; C118731:dronc protein, Drosophila