Evolutionary conservation of apoptosis mechanisms: lepidopteran and baculoviral inhibitor of apoptosis proteins are inhibitors of mammalian caspase-9.
We cloned a new inhibitor of apoptosis protein (IAP) homolog, SfIAP, from Spodoptera frugiperda Sf-21 cells, a host of insect baculoviruses. SfIAP contains two baculovirus IAP repeat domains followed by a RING domain. SfIAP has striking amino acid sequence similarity with baculoviral IAPs, CpIAP and OpIAP, suggesting that baculoviral IAPs may be host-derived genes. SfIAP and baculoviral CpIAP inhibit Bax but not Fas-induced apoptosis in human cells. Their apoptosis-suppressing activity in mammalian cells requires both baculovirus IAP repeat and RING domains. Further biochemical data suggest that SfIAP and CpIAP are specific inhibitors of mammalian caspase-9, the pinnacle caspase in the mitochondria/cytochrome c pathway for apoptosis, but are not inhibitors of downstream caspase-3 and caspase-7. Thus the mechanisms by which insect and baculoviral IAPs suppress apoptosis may involve inhibition of an insect caspase-9 homologue. Peptides representing the IAP-binding domain of the Drosophila cell death protein Grim abrogated human caspase suppression by SfIAP and CpIAP, implying evolutionary conservation of the functions of IAPs and their inhibitors.
Huang
Q
Q
Microbiology Program, Department of Entomology, University of California, One Shields Avenue, Davis, CA 95616, USA.
Deveraux
Q L
QL
Maeda
S
S
Salvesen
G S
GS
Stennicke
H R
HR
Hammock
B D
BD
Reed
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D016367:Baculoviridae / Q000737:chemistry; D053453:Caspase 9; D061945:Caspase Inhibitors; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors / Q000737:chemistry*; D019143:Evolution, Molecular; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins / Q000737:chemistry*; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000737:chemistry; D010446:Peptide Fragments / Q000494:pharmacology; D011506:Proteins; D016415:Sequence Alignment; D018411:Spodoptera / Q000737:chemistry*; D014764:Viral Proteins / Q000737:chemistry / Q000494:pharmacology
D001426:Bacterial Proteins; D061945:Caspase Inhibitors; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D009479:Neuropeptides; D010446:Peptide Fragments; D011506:Proteins; D014764:Viral Proteins; C108881:grim protein, Drosophila; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus; C506433:CASP9 protein, human; D053453:Caspase 9