CCAAT/Enhancer Binding Protein β Is a Neuronal Transcriptional Regulator Activated by Nerve Growth Factor Receptor Signaling

CCAAT/enhancer binding protein beta (C/EBPbeta) is a transcriptional regulator of the basic leucine zipper family. By in situ hybridization analysis, we found that C/EBPbeta is widely expressed in the CNS of adult mice, including cells of the hippocampus and dentate gyrus and cerebellar Purkinje and granule cells. Expression of C/EBPbeta had also been reported in the PC12 cell line, which undergoes differentiation to neuron-like cells in response to nerve growth factor (NGF). We show that C/EBPbeta mRNA expression increases while protein levels decrease during differentiation of PC12 cells. In transactivation assays, C/EBPbeta activity was stimulated by NGF receptor signaling. Mutations of a phosphorylation site for mitogen-activated protein kinase in C/EBPbeta affected its capacity to transactivate in a promoter-specific manner. Our data identify the C/EBPbeta protein and gene as direct downstream targets of the NGF receptor and suggest a role for C/EBPbeta in neurotrophin signaling in the brain.