Abstract |
Apoptosis is cellular suicide functionally opposite of mitosis. It plays an important role in tissue growth control and removal of damaged and premalignant cells. The decrease in death suppressor Bcl-2 protein level was implicated in the many types of apoptotic cell death. Because Bcl-2 protein was recently found to be cleaved during apoptosis induced by Fas ligation, IL-3 withdrawal, and alphavirus infection, we assessed whether Bcl-2 protein was also cleaved during the anticancer drug (VP-16)-induced apoptotic cell death in U937 cells. We found that Bcl-2 protein was cleaved in vivo and in vitro after the treatment of VP-16. We also found that caspase-3/CPP32, which was activated after VP-16 treatment, was responsible for the direct cleavage of Bcl-2 protein. The overexpression of the cleaved Bcl-2 fragment increased the sensitivity to VP-16 and promoted apoptotic cell death. Therefore, caspase-3/CPP32 accelerates VP-16-induced U937 cell apoptosis by cleaving death suppressor Bcl-2 protein to produce a death promoter Bcl-2 fragment.
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Authors | N Fujita, T Tsuruo |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 246
Issue 2
Pg. 484-8
(May 19 1998)
ISSN: 0006-291X [Print] United States |
PMID | 9610388
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents, Phytogenic
- DNA Primers
- Peptide Fragments
- Proto-Oncogene Proteins c-bcl-2
- Etoposide
- CASP3 protein, human
- Casp3 protein, mouse
- Caspase 3
- Caspases
- Cysteine Endopeptidases
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Topics |
- Animals
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Apoptosis
(drug effects, physiology)
- Base Sequence
- Caspase 3
- Caspases
- Cysteine Endopeptidases
(metabolism)
- DNA Primers
(genetics)
- Etoposide
(pharmacology)
- Genes, bcl-2
- HL-60 Cells
- Humans
- Mice
- Peptide Fragments
(genetics, metabolism, pharmacology)
- Polymerase Chain Reaction
- Proto-Oncogene Proteins c-bcl-2
(genetics, metabolism, pharmacology)
- Transfection
- Tumor Cells, Cultured
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