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

Emily H Y Cheng, David G. Kirsch, Rollie J. Clem, Rajani Ravi, Michael B. Kastan, Atul Bedi, Kazuyoshi Ueno, J Marie Hardwick

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1966-1968
Number of pages3
JournalScience
Volume278
Issue number5345
DOIs
StatePublished - Dec 12 1997

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Effector Caspases
Caspases
Apoptosis
Sindbis Virus
Cell Death
Interleukin-3
Caspase 3
Caspase 2
Cysteine Proteases
Ligation

ASJC Scopus subject areas

  • General

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Conversion of Bcl-2 to a bax-like death effector by caspases. / Cheng, Emily H Y; Kirsch, David G.; Clem, Rollie J.; Ravi, Rajani; Kastan, Michael B.; Bedi, Atul; Ueno, Kazuyoshi; Hardwick, J Marie.

In: Science, Vol. 278, No. 5345, 12.12.1997, p. 1966-1968.

Research output: Contribution to journalArticle

Cheng, EHY, Kirsch, DG, Clem, RJ, Ravi, R, Kastan, MB, Bedi, A, Ueno, K & Hardwick, JM 1997, 'Conversion of Bcl-2 to a bax-like death effector by caspases', Science, vol. 278, no. 5345, pp. 1966-1968. https://doi.org/10.1126/science.278.5345.1966
Cheng, Emily H Y ; Kirsch, David G. ; Clem, Rollie J. ; Ravi, Rajani ; Kastan, Michael B. ; Bedi, Atul ; Ueno, Kazuyoshi ; Hardwick, J Marie. / Conversion of Bcl-2 to a bax-like death effector by caspases. In: Science. 1997 ; Vol. 278, No. 5345. pp. 1966-1968.
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