Activation and degradation of the transcription factor C/EBP during long-term facilitation in Aplysia.
Long-term facilitation (LTF) of the sensory-to-motor synapses that mediate defensive reflexes in Aplysia requires induction of the transcription factor Aplysia CCAAT/enhancer binding protein (ApC/EBP) as an early response gene. We examined the time course of ApC/ EBP DNA binding during the induction of LTF: Binding activity was detected within 1 h of the sensitization treatment with serotonin, reached a maximum at 2 h, and decreased after 6 h. How are DNA binding and the turnover of ApC/EBP regulated? We find that phosphorylation of ApC/EBP by mitogen-activated protein (MAP) kinase is essential for binding. MAP kinase appears to be activated through protein kinase C. We also showed that ApC/EBP is degraded through the ubiquitin-proteasome pathway but that phosphorylation by MAP kinase renders it resistant to proteolysis. Thus, phosphorylation by MAP kinase is required for ApC/EBP to act as a transcription activator as well as to assure its stability early in the consolidation phase, when genes essential for the development of LTF begin to be expressed.
Yamamoto
N
N
Center for Neurobiology and Behavior, Columbia University College of Physicians & Surgeons, New York, New York 10032, USA.
Hegde
A N
AN
Chain
D G
DG
Schwartz
J H
JH
D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology*; D017952:Ganglia, Invertebrate / Q000378:metabolism; D017781:Genes, Immediate-Early; D020935:MAP Kinase Signaling System; D008568:Memory / Q000502:physiology*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D011493:Protein Kinase C / Q000502:physiology; D011499:Protein Processing, Post-Translational; D012701:Serotonin / Q000494:pharmacology; D014158:Transcription, Genetic; D014452:Ubiquitins / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009097:Multienzyme Complexes; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D014452:Ubiquitins; D012701:Serotonin; D004247:DNA; D011493:Protein Kinase C; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex