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

Science  12 Dec 1997:
Vol. 278, Issue 5345, pp. 1966-1968
DOI: 10.1126/science.278.5345.1966

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Abstract

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 Asp34 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.

  • * Present address: Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.

  • To whom correspondence should be addressed. E-mail: hardwick{at}welchlink.welch.jhu.edu

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