Granzyme A is an interleukin 1 beta-converting enzyme

J Exp Med. 1995 May 1;181(5):1917-22. doi: 10.1084/jem.181.5.1917.


Apoptosis is critically dependent on the presence of the ced-3 gene in Caenorhabditis elegans, which encodes a protein homologous to the mammalian interleukin (IL)-1 beta-converting enzyme (ICE). Overexpression of ICE or ced-3 promotes apoptosis. Cytotoxic T lymphocyte-mediated rapid apoptosis is induced by the proteases granzyme A and B. ICE and granzyme B share the rare substrate site of aspartic acid, after which amino acid cleavage of precursor IL-1 beta (pIL-1 beta) occurs. Here we show that granzyme A, but not granzyme B, converts pIL-1 beta to its 17-kD mature form. Major cleavage occurs at Arg120, four amino acids downstream of the authentic processing site, Asp116. IL-1 beta generated by granzyme A is biologically active. When pIL-1 beta processing is monitored in lipopolysaccharide-activated macrophage target cells attacked by cytotoxic T lymphocytes, intracellular conversion precedes lysis. Prior granzyme inactivation blocks this processing. We conclude that the apoptosis-inducing granzyme A and ICE share at least one downstream target substrate, i.e., pIL-1 beta. This suggests that lymphocytes, by means of their own converting enzyme, could initiate a local inflammatory response independent of the presence of ICE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apoptosis
  • Caspase 1
  • Cysteine Endopeptidases / metabolism*
  • Granzymes
  • Humans
  • Interleukin-1 / metabolism
  • Molecular Sequence Data
  • Protein Precursors / metabolism
  • Serine Endopeptidases / metabolism*


  • Interleukin-1
  • Protein Precursors
  • interleukin 1 precursor
  • Granzymes
  • Serine Endopeptidases
  • GZMA protein, human
  • Cysteine Endopeptidases
  • Caspase 1