Role of Bid-induced mitochondrial outer membrane permeabilization in granzyme B-induced apoptosis.
Cytotoxic lymphocytes (CL) induce death of their targets by granule exocytosis. During this process, enzymes contained within cytotoxic granules (granzymes) are delivered to the target cell where the enzymes trigger the cell death by cleaving specific substrates. Granzyme B is the only granzyme that has been shown to induce cell death by apoptosis, but the exact pathway by which this is achieved has been the subject of hot debate. Furthermore, several other death-inducing granzymes have been identified; therefore, the exact contribution of granzyme B to CL-induced death is unclear. In this study, we discuss our recent findings on granzyme B-induced cell death and discuss the potential relevance of this pathway to CL-induced death of viral-infected and transformed cells.
Waterhouse
Nigel J
NJ
Cancer Cell Death Laboratory, Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. nigel.waterhouse@petermac.org
Sedelies
Karin A
KA
Trapani
Joseph A
JA
D000818:Animals; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000494:pharmacology*; D053804:Granzymes; D051379:Mice; D051336:Mitochondrial Membranes / Q000502:physiology*; D010539:Permeability; D012697:Serine Endopeptidases / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000502:physiology*
D051023:BH3 Interacting Domain Death Agonist Protein; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases