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Research ArticleArticle

Role of Caspase 3-Dependent Bcl-2 Cleavage in Potentiation of Apoptosis by Bcl-2

Ye Liang, Karen D. Nylander, Chaohua Yan and Nina Felice Schor
Molecular Pharmacology January 2002, 61 (1) 142-149; DOI: https://doi.org/10.1124/mol.61.1.142
Ye Liang
The Pediatric Center for Neuroscience, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
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Karen D. Nylander
The Pediatric Center for Neuroscience, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
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Chaohua Yan
The Pediatric Center for Neuroscience, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
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Nina Felice Schor
The Pediatric Center for Neuroscience, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
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Abstract

Previous studies from our laboratory have demonstrated that Bcl-2 has a proapoptotic effect on neocarzinostatin (NCS)-treated PC12 pheochromocytoma cells. In the present study, we examine the mechanisms of this effect and demonstrate its relevance for the in vivo situation. Four hours after NCS treatment, a 23-kDa cleavage product of Bcl-2 was detected in whole cell lysates of bcl-2–transfected PC12 cells. In contrast, bcl-2 transfection protected PC12 cells from cisplatin-induced apoptosis, and cisplatin treatment did not result in Bcl-2 cleavage. Similarly, Bcl-2 cleavage did not occur and Bcl-2-mediated protection from, rather than potentiation of apoptosis was observed after NCS treatment of MCF-7 breast cancer cells. The caspase 3-specific inhibitor Ac-DEVD-CHO prevented Bcl-2 cleavage and attenuated NCS-induced apoptosis inbcl-2–transfected PC12 cells, whereas it had no effect on NCS-induced apoptosis in mock-transfected PC12 cells. Furthermore, MCF-7 cells do not express caspase 3, a finding in concert with the lack of Bcl-2 cleavage in this line. In in vivo experiments, xenografts of bcl-2–transfected PC12 cells were more susceptible to NCS toxicity than were xenografts of mock-transfected PC12 cells. Caspase 3-mediated Bcl-2 cleavage therefore plays an important role in the potentiation by Bcl-2 of NCS-induced apoptosis.

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Molecular Pharmacology: 61 (1)
Molecular Pharmacology
Vol. 61, Issue 1
1 Jan 2002
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Research ArticleArticle

Role of Caspase 3-Dependent Bcl-2 Cleavage in Potentiation of Apoptosis by Bcl-2

Ye Liang, Karen D. Nylander, Chaohua Yan and Nina Felice Schor
Molecular Pharmacology January 1, 2002, 61 (1) 142-149; DOI: https://doi.org/10.1124/mol.61.1.142

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Research ArticleArticle

Role of Caspase 3-Dependent Bcl-2 Cleavage in Potentiation of Apoptosis by Bcl-2

Ye Liang, Karen D. Nylander, Chaohua Yan and Nina Felice Schor
Molecular Pharmacology January 1, 2002, 61 (1) 142-149; DOI: https://doi.org/10.1124/mol.61.1.142
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