Conversion of Bcl-2 to a Bax-like death effector by caspases.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Cheng, EH; Kirsch, DG; Clem, RJ; Ravi, R; Kastan, MB; Bedi, A; Ueno, K; Hardwick, JM
Published Date
- December 12, 1997
Published In
Volume / Issue
- 278 / 5345
Start / End Page
- 1966 - 1968
PubMed ID
- 9395403
International Standard Serial Number (ISSN)
- 0036-8075
Digital Object Identifier (DOI)
- 10.1126/science.278.5345.1966
Language
- eng
Conference Location
- United States