Caspase activation by granzyme B is indirect, and caspase autoprocessing requires the release of proapoptotic mitochondrial factors
- Author(s)
- Sutton, VR; Wowk, ME; Cancilla, M; Trapani, JA;
- Details
- Publication Year 2003-03,Volume 18,Issue #3,Page 319-329
- Journal Title
- IMMUNITY
- Publication Type
- Journal Article
- Abstract
- Apoptosis in response to granzyme B involves activation of caspase-dependent target cell death pathways. Herein, we show that granzyme B initiates caspase processing but cannot fully process procaspase-3 in intact Jurkat T leukemia or NT2 neuronal cells. Rather, the release from mitochondria of proapoptotic mediators cytochrome c, Smac/Diablo, and HtrA2/Omi facilitates full activation of caspases that results from auto-processing. Bcl-2 overexpression in mitochondria suppresses the release of these proapoptotic molecules, resulting in cell survival despite partial procaspase processing by granzyme B. We propose that binding of inhibitor of apoptosis (IAP) proteins to partially processed procaspases inhibits cell death unless mitochondrial disruption also occurs in response to granzyme B or activated BH3-domain proteins such as truncated Bid.
- Publisher
- CELL PRESS
- Keywords
- CYTOCHROME-C RELEASE; PERFORIN-DEFICIENT MICE; STRUCTURAL BASIS; CELL-DEATH; CYTOTOXIC LYMPHOCYTES; PROMOTES APOPTOSIS; DNA FRAGMENTATION; SERINE-PROTEASE; DIRECT CLEAVAGE; PORE FORMATION
- Publisher's Version
- https://doi.org/10.1016/S1074-7613(03)00050-5
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2003-03-01 12:00:00