Conversion of Bcl-2 to a Bax-like death effector by caspases.

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

Language

  • eng

Conference Location

  • United States