Conversion of Bc1-2 to a Bax-like Death Effector by Caspases

Caspases are a family of cysteine proteases implicated in the biochemical and morphological changes that occur during apoptosis (programmed cell death). The loop domain of Bcl-2 is cleaved at Asp$^{34}$ by caspase-3 (CPP32) in vitro, in cells overexpressing caspase-3, and after induction of apoptosi...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1997-12, Vol.278 (5345), p.1966-1968
Main Authors: Emily H.-Y. Cheng, Kirsch, David G., Clem, Rollie J., Ravi, Rajani, Kastan, Michael B., Bedi, Atul, Ueno, Kazuyoshi, Hardwick, J. Marie
Format: Article
Language:English
Subjects:
Antibodies
Apoptosis
Cell death
Cell lines
Cellular immunity
COS cells
Kidney cells
Plasmids
T lymphocytes
Viability
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Summary:Caspases are a family of cysteine proteases implicated in the biochemical and morphological changes that occur during apoptosis (programmed cell death). The loop domain of Bcl-2 is cleaved at Asp$^{34}$ by caspase-3 (CPP32) in vitro, in cells overexpressing caspase-3, and after induction of apoptosis by Fas ligation and interleukin-3 withdrawal. The carboxyl-terminal Bcl-2 cleavage product triggered cell death and accelerated Sindbis virus-induced apoptosis, which was dependent on the BH3 homology and transmembrane domains of Bcl-2. Inhibitor studies indicated that cleavage of Bcl-2 may further activate downstream caspases and contribute to amplification of the caspase cascade. Cleavage-resistant mutants of Bcl-2 had increased protection from interleukin-3 withdrawal and Sindbis virus-induced apoptosis. Thus, cleavage of Bcl-2 by caspases may ensure the inevitability of cell death.
ISSN:0036-8075
1095-9203