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

TY - JOUR

T1 - CREB-dependent Nur77 induction following depolarization in PC12 cells and neurons is modulated by MEF2 transcription factors

AU - Lam, Brian Yee Hong

AU - Zhang, Wenting

AU - Ng, David Chi-Heng

AU - Maruthappu, Mahiben

AU - Roderick, Hywel Llewelyn

AU - Chawla, Sangeeta

PY - 2010/2

Y1 - 2010/2

N2 - 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.

AB - 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.

KW - Animals

KW - CREB-Binding Protein

KW - Calcium

KW - Cells, Cultured

KW - Cyclosporine

KW - Enzyme Inhibitors

KW - Gene Expression Regulation

KW - Green Fluorescent Proteins

KW - Hippocampus

KW - Humans

KW - Mice

KW - Mutation

KW - Myogenic Regulatory Factors

KW - NFATC Transcription Factors

KW - Neurons

KW - Nuclear Receptor Subfamily 4, Group A, Member 1

KW - PC12 Cells

KW - Potassium Chloride

KW - Promoter Regions, Genetic

KW - Rats

KW - Time Factors

KW - Transfection

UR - http://www.scopus.com/inward/record.url?scp=75149163016&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2009.06521.x

DO - 10.1111/j.1471-4159.2009.06521.x

M3 - Article

C2 - 19968756

VL - 112

SP - 1065

EP - 1073

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 4

ER -