CREB is cleaved by caspases during neural cell apoptosis.
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.
François
F
F
Institute of Molecular Biosciences, Massey University, Private Bag 11222, Palmerston North, New Zealand.
Godinho
M J
MJ
Grimes
M L
ML
D000255:Adenosine Triphosphate / Q000378:metabolism; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003574:Cytochrome c Group / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D017362:Cyclic AMP Response Element-Binding Protein; D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D014157:Transcription Factors; C108637:aspartyl-glutamyl-valyl-aspartal; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D000255:Adenosine Triphosphate; C505407:CASP3 protein, human; C506433:CASP9 protein, human; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D019311:Staurosporine