CREB-dependent Nur77 induction following depolarization in PC12 cells and neurons is modulated by MEF2 transcription factors

Brian Yee Hong Lam, Wenting Zhang, David Chi-Heng Ng, Mahiben Maruthappu, Hywel Llewelyn Roderick, Sangeeta Chawla

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)1065-1073
Number of pages9
JournalJournal of Neurochemistry
Issue number4
Publication statusPublished - Feb 2010


  • Animals
  • CREB-Binding Protein
  • Calcium
  • Cells, Cultured
  • Cyclosporine
  • Enzyme Inhibitors
  • Gene Expression Regulation
  • Green Fluorescent Proteins
  • Hippocampus
  • Humans
  • Mice
  • Mutation
  • Myogenic Regulatory Factors
  • NFATC Transcription Factors
  • Neurons
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • PC12 Cells
  • Potassium Chloride
  • Promoter Regions, Genetic
  • Rats
  • Time Factors
  • Transfection

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