CREB-dependent Nur77 induction following depolarization in PC12 cells and neurons is modulated by MEF2 transcription factors.
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.
Lam
Brian Yee Hong
BY
Department of Pharmacology, University of Cambridge, Cambridge, UK.
Zhang
Wenting
W
Ng
David Chi-Heng
DC
Maruthappu
Mahiben
M
Roderick
Hywel Llewelyn
HL
Chawla
Sangeeta
S
D000818:Animals; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D004791:Enzyme Inhibitors; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D064326:MEF2 Transcription Factors; D051379:Mice; D009154:Mutation / Q000502:physiology; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D013997:Time Factors; D014162:Transfection / Q000379:methods
D004791:Enzyme Inhibitors; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D050778:NFATC Transcription Factors; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D049452:Green Fluorescent Proteins; D011189:Potassium Chloride; D016572:Cyclosporine; D050882:CREB-Binding Protein; D002118:Calcium