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Papers In Press, published online ahead of print March 17, 2004
Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002
Corresponding Author: mark.smyth{at}petermac.org
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 over-expression 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.
J. Biol. Chem, 10.1074/jbc.M401670200
Submitted on February 16, 2004
Revised on March 12, 2004
Accepted on March 17, 2004
Granzyme M mediates a novel form of perforin-dependent cell death
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