Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor.
The promoter regions of several phorbol diester-(TPA-) inducible genes (collagenase, stromelysin, hMT IIA, and SV40) share a conserved 9 bp motif. Synthetic copies of these closely related sequences conferred TPA inducibility upon heterologous promoters. Footprinting analysis indicated that these TPA-responsive elements (TREs) are recognized by a common cellular protein: the previously described transcription factor AP-1. A point mutation that eliminated the basal and induced activity of the TRE also interfered with its ability to bind AP-1. Treatment of cultured cells with TPA led to a rapid 3- to 4-fold increase in TRE binding activity, by a posttranslational mechanism. These results strongly suggest that AP-1 is at the receiving end of a complex pathway responsible for transmitting the effects of phorbol ester tumor promoters from the plasma membrane to the transcriptional machinery.
D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics*; D010450:Endopeptidases / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects*; D005809:Genes, Regulator; D006801:Humans; D019278:Matrix Metalloproteinase 3; D008668:Metallothionein / Q000235:genetics; D003012:Microbial Collagenase / Q000235:genetics; D011401:Promoter Regions, Genetic; D051381:Rats; D013539:Simian virus 40 / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D014157:Transcription Factors; D008668:Metallothionein; D010450:Endopeptidases; D019278:Matrix Metalloproteinase 3; D003012:Microbial Collagenase; D013755:Tetradecanoylphorbol Acetate