Action of NF-kappaB on the delta opioid receptor gene promoter |
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Authors: | Chen Yulong L Law Ping-Yee Loh Horace H |
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Institution: | Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. chenx112@tc.umn.edu |
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Abstract: | The G protein-coupled delta opioid receptor gene (dor) is temporally and spatially expressed during development. The DOR receptor plays important roles in diverse biological processes, including pain control, immune functions, and cell survival. We previously found that PI3K/Akt/NF-kappaB signaling is important in the regulation of dor gene expression during nerve growth factor (NGF)-induced differentiation of PC12h cells, which prompted us to examine whether NF-kappaB p65 is directly or indirectly involved in the regulation of dor promoter activity. In this study, deletional and functional analysis of the dor promoter revealed a 94-bp NGF-responsive fragment upstream of the dor promoter region and involvement of NF-kappaB in regulating the promoter activity. Chromatin immunoprecipitation assays demonstrated that NF-kappaB p65 is directly bound to the dor promoter and such binding is related to NGF/PI3K signaling. Together, the results show that direct association of p65 with the promoter is important in NGF-induced dor promoter activity. |
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Keywords: | AP-1 activator protein 1 AP-2 activator protein 2 CREB cyclic AMP-response element binding protein dor delta opioid receptor gene NF-κB nuclear factor κB NGF nerve growth factor PI3K phosphatidylinositol 3-kinase |
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