Abstract
The REtsAF cell line expresses a temperature-sensitive mutant of the SV40 large tumor antigen. At restrictive temperature (39.5 degrees C), the cells undergo p53-mediated apoptosis, which can be inhibited by Bcl-2. Here, we show that Z-VAD-fmk, a caspase inhibitor, can suppress the Bcl-2-dependent cell survival at 39.5 degrees C. This result suggests that a caspase-like activity can act as an inhibitor of apoptosis in this model, downstream of Bcl-2. Our results also suggest that this activity may be up-regulated by Bcl-2 and may be responsible for cleavage of the tumor suppressor Rb protein.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Chloromethyl Ketones / pharmacology
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Animals
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Apoptosis*
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Blotting, Western
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Caspase Inhibitors*
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Cell Line
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Cell Survival / drug effects*
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Cysteine Proteinase Inhibitors / pharmacology
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Fibroblasts / metabolism
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Genes, bcl-2 / drug effects*
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Oligopeptides / pharmacology
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Rats
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Signal Transduction
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Staurosporine / pharmacology
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Temperature
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Tetracycline / pharmacology
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Time Factors
Substances
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Amino Acid Chloromethyl Ketones
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Caspase Inhibitors
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Cysteine Proteinase Inhibitors
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Enzyme Inhibitors
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N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone
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Oligopeptides
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benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone
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benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
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Tetracycline
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Staurosporine