Granzyme M Mediates a Novel Form of Perforin-dependent Cell Death Academic Article uri icon


  • Cell death is mediated by cytotoxic lymphocytes through various granule serine proteases released with perforin. The unique protease activity, restricted expression, and distinct gene locus of granzyme M suggested this enzyme might have a novel biological function or trigger a novel form of cell death. Herein, we demonstrate that in the presence of perforin, the protease activity of granzyme M rapidly and effectively induces target cell death. In contrast to granzyme B, cell death induced by granzyme M does not feature obvious DNA fragmentation, occurs independently of caspases, caspase activation, and perturbation of mitochondria and is not inhibited by overexpression of Bcl-2. These data raise the likelihood that granzyme M represents a third major and specialized perforin-dependent cell death pathway that plays a significant role in death mediated by NK cells.


  • Kelly, Janice M
  • Waterhouse, Nigel J
  • Cretney, Erika
  • Browne, Kylie A
  • Ellis, Sarah
  • Trapani, Joseph A
  • Smyth, Mark J

publication date

  • May 21, 2004

has subject area