Abstract
Expression of the nuclear orphan receptor gene Nur77 in neuronal cells is induced by activity-dependent increases in intracellular Ca2+ ions. Ca2+ responsiveness of the Nur77 gene has been attributed to two distinct DNA regulatory regions that recruit the transcription factors cAMP response element binding protein (CREB) and myocyte enhancer factor-2 (MEF2). Here we used dominant interfering and constitutively active mutants of CREB and MEF2 proteins to assess their relative contribution to depolarization-induced Nur77 expression in undifferentiated PC12 cells and hippocampal neurons. We show that while CREB is necessary for Ca2+-activated Nur77 expression MEF2 functions to modulate CREB-dependent Nur77 expression by acting as a repressor in quiescent cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CREB-Binding Protein / genetics
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CREB-Binding Protein / metabolism
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Calcium / metabolism
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Cells, Cultured
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Cyclosporine / pharmacology
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Enzyme Inhibitors
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology*
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Green Fluorescent Proteins / genetics
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Hippocampus / cytology
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Humans
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MEF2 Transcription Factors
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Mice
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Mutation / physiology
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Myogenic Regulatory Factors / genetics
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Myogenic Regulatory Factors / metabolism*
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NFATC Transcription Factors / metabolism
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Neurons / drug effects
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Neurons / metabolism*
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Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics
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Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism*
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PC12 Cells / drug effects
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PC12 Cells / metabolism
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Potassium Chloride / pharmacology
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Promoter Regions, Genetic / genetics
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Rats
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Time Factors
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Transfection / methods
Substances
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Enzyme Inhibitors
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MEF2 Transcription Factors
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Myogenic Regulatory Factors
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NFATC Transcription Factors
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Nuclear Receptor Subfamily 4, Group A, Member 1
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Green Fluorescent Proteins
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Potassium Chloride
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Cyclosporine
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CREB-Binding Protein
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Calcium