Format

Send to

Choose Destination
Immunity. 2003 Mar;18(3):319-29.

Caspase activation by granzyme B is indirect, and caspase autoprocessing requires the release of proapoptotic mitochondrial factors.

Author information

1
Cancer Immunology Program, Peter MacCallum Cancer Institute, Locked Bag 1, A'Beckett Street, 8006, Melbourne, Australia.

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 autoprocessing. 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.

PMID:
12648450
DOI:
10.1016/s1074-7613(03)00050-5
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center