Regulation of transcription factor AP-2 by the morphogen retinoic acid and by second messengers.
The expression of the transcription factor AP-2 recently has been shown to be enhanced during retinoic acid (RA)-induced differentiation of NT2 cells, a human teratocarcinoma cell line. Here we show that this induction of AP-2 mRNA is at the level of transcription and is transient, reaching a peak 48-72 hr after the addition of RA and declining thereafter, even in the continuous presence of RA. Increased levels of AP-2 mRNA are reflected in a similar elevation of AP-2 protein and accompanied by an increase in the AP-2-binding site-dependent transcriptional activity of a reporter gene. AP-2 also has been proposed to confer TPA and cAMP inducibility on promoters/enhancers containing AP-2-binding sites. We investigated the effect of these agents on the expression of AP-2 protein and mRNA. Our experiments demonstrate that expression of the AP-2 gene in HeLa cells is not elevated significantly by TPA or by a calcium ionophore and is not enhanced at all by agents that increase intracellular cAMP concentration. In fact, AP-2 mRNA is repressed by both TPA and the calcium ionophore A23187 through a delayed response. These data suggest that the AP-2-binding site-mediated cAMP and TPA responses are not regulated at the level of AP-2 expression but, rather, achieved either by post-translational changes in AP-2 or in conjunction with another protein.
Lüscher
B
B
Howard Hughes Medical Institute, Department of Biochemistry, University of California, Berkeley 94720.
Mitchell
P J
PJ
Williams
T
T
Tjian
R
R
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D015153:Blotting, Western; D000001:Calcimycin / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D010957:Plasmids; D012333:RNA, Messenger / Q000187:drug effects; D015290:Second Messenger Systems; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*
D015342:DNA Probes; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D005576:Colforsin; D000001:Calcimycin; D014212:Tretinoin; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine