Granzyme M mediates a novel form of perforin-dependent cell death

被引:107
作者
Kelly, JM [1 ]
Waterhouse, NJ [1 ]
Cretney, E [1 ]
Browne, KA [1 ]
Ellis, S [1 ]
Trapani, JA [1 ]
Smyth, MJ [1 ]
机构
[1] Peter MacCallum Canc Ctr, Canc Immunol Program, Melbourne, Vic 8006, Australia
关键词
D O I
10.1074/jbc.M401670200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:22236 / 22242
页数:7
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