Cloning and characterization of an inhibitor of apoptosis protein (IAP) from Bombyx mori.
We cloned a novel inhibitor of apoptosis protein (IAP) family member, BmIAP, from Bombyx mori BmN cells. BmIAP contains two baculoviral IAP repeat (BIR) domains followed by a RING domain. BmIAP shares striking amino acid sequence similarity with lepidopteran IAPs, SfIAP and TnIAP, and with two baculoviral IAPs, CpIAP and OpIAP, suggesting evolutionary conservation. BmIAP blocks programmed cell death (apoptosis) in Spodoptera frugiperda Sf-21 cells induced by p35 deficient Autographa californica nucleopolyhedrovirus (AcMNPV). This anti-apoptotic function requires both the BIR domains and RING domain of BmIAP. In mammalian cells, BmIAP inhibits Bax induced but not Fas induced apoptosis. Further biochemical data suggest that BmIAP is a specific inhibitor of mammalian caspase-9, an initiator caspase in the mitochondria/cytochrome-c pathway, but not the downstream effector proteases, caspase-3 and caspase-7. These results suggest that suppression of apoptosis by lepidopteran IAPs in insect cells may involve inhibition of an upstream initiator caspase in the conserved mitochondria/cytochrome-c pathway for apoptosis.
Huang
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Q
Department of Entomology, University of California, Davis 95616, USA.
Deveraux
Q L
QL
Maeda
S
S
Stennicke
H R
HR
Hammock
B D
BD
Reed
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D016367:Baculoviridae / Q000235:genetics; D001483:Base Sequence; D012831:Bombyx / Q000235:genetics*; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D018411:Spodoptera; D051028:bcl-2-Associated X Protein
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C111892:DIAP2 protein, Drosophila; D017931:DNA Primers; D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D053453:Caspase 9; D020169:Caspases