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  • Title: Granzyme M mediates a novel form of perforin-dependent cell death.
    Author: Kelly JM, Waterhouse NJ, Cretney E, Browne KA, Ellis S, Trapani JA, Smyth MJ.
    Journal: J Biol Chem; 2004 May 21; 279(21):22236-42. PubMed ID: 15028722.
    Abstract:
    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.
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