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Molecular Cloning, Expression, and Characterization of Rat Homolog of Human AP-2 That Stimulates Neuropeptide Y Transcription Activity in Response to Nerve Growth Factor

Laboratory of Neurochemistry (B.-S.L., P.R.K.) Laboratory of Adaptive Systems (W.Z.) NINDS National Institutes of Health Bethesda, Maryland 20892-4130 Center for Bio/Molecular Science and Engineering, (W.M., D.A.S.), Naval Research Laboratory Washington, D.C. 20375 Endocrinology and Behavior Branch (L.Z.) National Institute of Mental Health National Institutes of Health Bethesda, Maryland 20892

Neuropeptide Y (NPY) plays an important role in the central regulation of neuronal activity, endocrine and sexual behavior, and food intake. Although transcription activity of the NPY gene in PC12 cells is regulated by a number of agents such as nerve growth factor (NGF), the mechanism responsible for the NGF-elicited increase in the transcription of the NPY gene remains to be explored. In this study, we isolated and characterized a nuclear protein that is bound to NGF-response elements (NGFRE) that lie between nucleotide -87 and -33 of the rat NPY promoter gene. This nuclear protein is identical to the rat homolog of human transcription factor AP-2. We further demonstrated that rat AP-2 promotes efficient NPY transcription activity in response to NGF. Finally, we provide direct evidence that the mice lacking transcription factor AP-2 exhibit reduced expression of NPY mRNA compared with wild-type mice, further supporting the hypothesis that AP-2 is an important transcription factor in regulating NPY transcription activity.

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