cAMP-dependent regulation of proenkephalin by JunD and JunB: positive and negative effects of AP-1 proteins.
We demonstrate that JunD, a component of the AP-1 transcription factor complex, activates transcription of the human proenkephalin gene in a fashion that is completely dependent upon the cAMP-dependent protein kinase, protein kinase A. Activation of proenkephalin transcription by JunD is dependent upon a previously characterized cAMP-, phorbol ester-, and Ca(2+)-inducible enhancer, and JunD is shown to bind the enhancer as a homodimer. Another component of the AP-1 transcription complex, JunB, is shown to inhibit activation mediated by JunD. As a homodimer JunB is unable to bind the enhancer; however in the presence of c-Fos, high-affinity binding is observed. Furthermore, JunD is shown to activate transcription of genes linked to both cAMP and phorbol ester response elements in a protein kinase A-dependent fashion, further blurring the distinction between these response elements. These results demonstrate that the transcriptional activity of an AP-1-related protein is regulated by the cAMP-dependent second-messenger pathway and suggest that JunD and other AP-1-related proteins may play an important role in the regulation of gene expression by cAMP-dependent intracellular signaling pathways.
Kobierski
L A
LA
Laboratory of Molecular Neurobiology, Massachusetts General Hospital, Charlestown 02129.
Chu
H M
HM
Tan
Y
Y
Comb
M J
MJ
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D004745:Enkephalins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D005910:Glioma; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D012156:Reticulocytes / Q000378:metabolism; D015290:Second Messenger Systems; D015533:Transcriptional Activation; D014162:Transfection
D004745:Enkephalins; D009838:Oligodeoxyribonucleotides; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; C029992:proenkephalin; D005576:Colforsin; D000242:Cyclic AMP; D011494:Protein Kinases; D015056:1-Methyl-3-isobutylxanthine