Evolutionary conservation of apoptosis mechanisms: lepidopteran and baculoviral inhibitor of apoptosis proteins are inhibitors of mammalian caspase-9

Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1427-32. doi: 10.1073/pnas.97.4.1427.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics*
  • Baculoviridae / chemistry
  • Caspase 9
  • Caspase Inhibitors*
  • Cell Line
  • Cells, Cultured
  • Cloning, Molecular
  • Drosophila Proteins*
  • Enzyme Inhibitors / chemistry*
  • Evolution, Molecular
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Insect Proteins / chemistry*
  • Molecular Sequence Data
  • Neuropeptides / chemistry
  • Peptide Fragments / pharmacology
  • Proteins*
  • Sequence Alignment
  • Spodoptera / chemistry*
  • Viral Proteins / chemistry
  • Viral Proteins / pharmacology

Substances

  • Bacterial Proteins
  • Caspase Inhibitors
  • Drosophila Proteins
  • Enzyme Inhibitors
  • Inhibitor of Apoptosis Proteins
  • Insect Proteins
  • Neuropeptides
  • Peptide Fragments
  • Proteins
  • Viral Proteins
  • grim protein, Drosophila
  • inhibitor of apoptosis, Nucleopolyhedrovirus
  • CASP9 protein, human
  • Caspase 9

Associated data

  • GENBANK/AF186378