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Hsp70 exerts its anti‐apoptotic function downstream of caspase‐3‐like proteases

Hsp70 exerts its anti‐apoptotic function downstream of caspase‐3‐like proteases The major heat shock protein, Hsp70, is an effective inhibitor of apoptosis. To study its mechanism of action, we created tumor cell lines with altered Hsp70 levels. The expression levels of Hsp70 in the cells obtained correlated well with their survival following treatments with tumor necrosis factor, staurosporine and doxorubicin. Surprisingly, the surviving Hsp70‐expressing cells responded to the apoptotic stimuli by activation of stress‐activated protein kinases, generation of free radicals, early disruption of mitochondrial transmembrane potential, release of cytochrome c from mitochondria and activation of caspase‐3‐like proteases in a manner essentially similar to that of the dying cells with low Hsp70 levels. However, Hsp70 inhibited late caspase‐dependent events such as activation of cytosolic phospholipase A2 and changes in nuclear morphology. Furthermore, Hsp70 conferred significant protection against cell death induced by enforced expression of caspase‐3. Thus, Hsp70 rescues cells from apoptosis later in the death signaling pathway than any known anti‐apoptotic protein, making it a tempting target for therapeutic interventions. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The EMBO Journal Wiley

Hsp70 exerts its anti‐apoptotic function downstream of caspase‐3‐like proteases

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References (60)

Publisher
Wiley
Copyright
Copyright © 2013 Wiley Periodicals, Inc
ISSN
0261-4189
eISSN
1460-2075
DOI
10.1093/emboj/17.21.6124
pmid
9799222
Publisher site
See Article on Publisher Site

Abstract

The major heat shock protein, Hsp70, is an effective inhibitor of apoptosis. To study its mechanism of action, we created tumor cell lines with altered Hsp70 levels. The expression levels of Hsp70 in the cells obtained correlated well with their survival following treatments with tumor necrosis factor, staurosporine and doxorubicin. Surprisingly, the surviving Hsp70‐expressing cells responded to the apoptotic stimuli by activation of stress‐activated protein kinases, generation of free radicals, early disruption of mitochondrial transmembrane potential, release of cytochrome c from mitochondria and activation of caspase‐3‐like proteases in a manner essentially similar to that of the dying cells with low Hsp70 levels. However, Hsp70 inhibited late caspase‐dependent events such as activation of cytosolic phospholipase A2 and changes in nuclear morphology. Furthermore, Hsp70 conferred significant protection against cell death induced by enforced expression of caspase‐3. Thus, Hsp70 rescues cells from apoptosis later in the death signaling pathway than any known anti‐apoptotic protein, making it a tempting target for therapeutic interventions.

Journal

The EMBO JournalWiley

Published: Feb 2, 1998

Keywords: ; ; ; ;

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