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

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.

journal_name

Immunity

journal_title

Immunity

authors

Sutton VR,Wowk ME,Cancilla M,Trapani JA

doi

10.1016/s1074-7613(03)00050-5

keywords:

subject

Has Abstract

pub_date

2003-03-01 00:00:00

pages

319-29

issue

3

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(03)00050-5

journal_volume

18

pub_type

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