CCAAT/enhancer binding protein beta 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.
Sterneck
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Eukaryotic Transcriptional Regulation Group, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
Johnson
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PF
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000166:cytology / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017403:In Situ Hybridization; D051379:Mice; D009154:Mutation; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016716:PC12 Cells; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017475:Receptors, Nerve Growth Factor / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D009414:Nerve Growth Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D014157:Transcription Factors; D017871:Calcium-Calmodulin-Dependent Protein Kinases