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 facto r Aplysia CCAAT/enhancer binding protein (ApC/EBP) as an early response gen e. 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 treat ment with serotonin, reached a maximum at 2 h, and decreased after 6 h. How are DIVA binding and the turnover of ApC/EBP regulated? We find that phosp horylation of ApC/EBP by mitogen-activated protein (MAP) kinase is essentia l for binding. MAP kinase appears to be activated through protein kinase C. We also showed that ApC/EBP is degraded through the ubiquitin-proteasome p athway but that phosphorylation by MAP kinase renders it resistant to prote olysis. 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 th e consolidation phase, when genes essential for the development of LTF begi n to be expressed.