Apoptosis in motion. An apical, P35-insensitive caspase mediates programmed cell death in insect cells

J Biol Chem. 2001 May 18;276(20):16704-10. doi: 10.1074/jbc.M010179200. Epub 2001 Feb 23.


Activation of caspases by proteolytic processing is a critical step during apoptosis in metazoans. Here we use high resolution time lapse microscopy to show a tight link between caspase activation and the morphological events delineating apoptosis in cultured SF21 cells from the moth Spodoptera frugiperda, a model insect system. The principal effector caspase, Sf-caspase-1, is proteolytically activated during SF21 apoptosis. To define the potential role of initiator caspases in vivo, we tested the effect of cell-permeable peptide inhibitors on pro-Sf-caspase-1 processing. Anti-caspase peptide analogues prevented apoptosis induced by diverse signals, including UV radiation and baculovirus infection. IETD-fmk potently inhibited the initial processing of pro-Sf-caspase-1 at the junction (TETD-G) of the large and small subunit, a cleavage that is blocked by inhibitor of apoptosis Op-IAP but not pancaspase inhibitor P35. Because Sf-caspase-1 was inhibited poorly by IETD-CHO, our data indicated that the protease responsible for the first step in pro-Sf-caspase-1 activation is a distinct apical caspase. Thus, Sf-caspase-1 activation is mediated by a novel, P35-resistant caspase. These findings support the hypothesis that apoptosis in insects, like that in mammals, involves a cascade of caspase activations.

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 / physiology*
  • Apoptosis / radiation effects
  • Bacterial Proteins / metabolism
  • Baculoviridae
  • Caspase 1 / chemistry
  • Caspase 1 / metabolism*
  • Cell Line
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Enzyme Precursors / chemistry
  • Enzyme Precursors / metabolism
  • Inhibitor of Apoptosis Proteins
  • Insect Proteins*
  • Moths
  • Oligopeptides / pharmacology*
  • Protein Subunits
  • Proteins*
  • Spodoptera
  • Transfection
  • Ultraviolet Rays
  • Viral Proteins / metabolism*


  • Bacterial Proteins
  • Cysteine Proteinase Inhibitors
  • Enzyme Precursors
  • Inhibitor of Apoptosis Proteins
  • Insect Proteins
  • Oligopeptides
  • Protein Subunits
  • Proteins
  • Viral Proteins
  • inhibitor of apoptosis, Nucleopolyhedrovirus
  • isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone
  • Caspase 1