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Published on: June 15, 2017
CREB-dependent Nur77 induction following depolarization in PC12 cells and neurons is modulated by MEF2 transcription
Brian Yee Hong Lam1, Wenting Zhang, David Chi-Heng Ng
1Department of Pharmacology, University of Cambridge, Cambridge, UK.
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.
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