Abstract
Programmed cell death, or apoptosis, is a tightly regulated process mediated by selective cleavage of proteins by caspases, resulting in ordered destruction of the cell. In addition to structural proteins, proteins that mediate anti-apoptotic signal transduction are also substrates; their destruction eliminates potential futile attempts to escape execution. We asked whether cAMP response element binding protein (CREB), a transcription factor that mediates nerve growth factor (NGF) survival signals, is a target for caspases during apoptosis. CREB was specifically cleaved by caspases in neuroblastoma extracts, and in cells induced to undergo apoptosis by staurosporine. The destruction of CREB eliminates a key factor that could reverse apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / metabolism
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Amino Acid Chloromethyl Ketones / pharmacology
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Animals
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Apoptosis*
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Caspase 3
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Caspase 9
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Caspase Inhibitors
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Caspases / metabolism*
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Cyclic AMP Response Element-Binding Protein / metabolism*
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Cytochrome c Group / metabolism
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Cytochrome c Group / pharmacology
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Enzyme Inhibitors / pharmacology
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Humans
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Neuroblastoma / metabolism
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Oligopeptides / pharmacology
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PC12 Cells
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Rats
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Signal Transduction / drug effects
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Staurosporine / pharmacology
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Transcription Factors / metabolism
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Tumor Cells, Cultured
Substances
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Amino Acid Chloromethyl Ketones
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Caspase Inhibitors
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Cyclic AMP Response Element-Binding Protein
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Cytochrome c Group
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Enzyme Inhibitors
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Oligopeptides
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Transcription Factors
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aspartyl-glutamyl-valyl-aspartal
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benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
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Adenosine Triphosphate
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CASP3 protein, human
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CASP9 protein, human
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Casp3 protein, rat
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Casp9 protein, rat
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Caspase 3
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Caspase 9
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Caspases
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Staurosporine