Molecular cloning, expression, and characterization of rat homolog of human AP-2alpha that stimulates neuropeptide Y transcription activity in response to nerve growth factor.
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-2alpha. We further demonstrated that rat AP-2a promotes efficient NPY transcription activity in response to NGF. Finally, we provide direct evidence that the mice lacking transcription factor AP-2alpha exhibit reduced expression of NPY mRNA compared with wild-type mice, further supporting the hypothesis that AP-2alpha is an important transcription factor in regulating NPY transcription activity.
Li
B S
BS
Laboratory of Neurochemistry, NINDS, National Institutes of Health Bethesda, Maryland 20892-4130, USA.
Kramer
P R
PR
Zhao
W
W
Ma
W
W
Stenger
D A
DA
Zhang
L
L
D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009478:Neuropeptide Y / Q000235:genetics*; D016716:PC12 Cells; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020218:Response Elements; D017385:Sequence Homology; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D004268:DNA-Binding Proteins; D009478:Neuropeptide Y; D012333:RNA, Messenger; C493673:TFAP2A protein, human; C493668:Tfap2a protein, mouse; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D004247:DNA; D020932:Nerve Growth Factor