Regulation of the human atrial natriuretic peptide gene in atrial cardiocytes by the transcription factor AP-1.
The effects of overexpression of individual components of the AP-1 transcription complex (ie, c-fos and c-jun) were examined in neonatal rat atriocyte cultures. Cotransfection of a c-jun expression plasmid together with a test plasmid linking portions of the human atrial natriuretic peptide (hANP) gene promoter to a bacterial chloramphenicol acetyl transferase (CAT) reporter resulted in a dramatic increase in ANP gene promoter activity. This effect appeared to operate through a consensus TPA (phorbol 12-myristate 13-acetate) response element (ie, AP-1 binding site) located approximately 235 base pairs upstream from the start site of transcription. This same TPA response element appears to be responsible for induction of hANP gene promoter activity by the phorbol ester TPA. Cotransfection of the same hANP promoter-CAT reporter constructs with a c-fos expression vector resulted in an unpredicted inhibition of reporter gene expression. This inhibitory activity was localized to the carboxy terminus of the c-fos protein and dominated the more conventional AP-1-dependent activity located elsewhere in the c-fos molecule. These findings suggest potential mechanisms for linking regulatory signals operative at or near the cell surface to the control of transcriptional activity in the cell nucleus.
Kovacic-Milivojevic
B
B
Metabolic Research Unit, University of California, San Francisco 94143.
Gardner
D G
DG
D009320:Atrial Natriuretic Factor / Q000235:genetics*; D001483:Base Sequence; D002478:Cells, Cultured; D015870:Gene Expression; D005786:Gene Expression Regulation; D016762:Genes, fos; D016758:Genes, jun; D006321:Heart / Q000502:physiology*; D006325:Heart Atria; D006801:Humans; D008668:Metallothionein / Q000235:genetics; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology; D010957:Plasmids; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D016755:Proto-Oncogene Proteins c-jun; D009320:Atrial Natriuretic Factor; D008668:Metallothionein; D013755:Tetradecanoylphorbol Acetate