ETS sites in the promoters of the matrix metalloproteinases collagenase (MMP-1) and stromelysin (MMP-3) are auxiliary elements that regulate basal and phorbol-induced transcription.
The matrix metalloproteinases collagenase (MMP-1) and stromelysin (MMP-3) are often coordinately expressed, and their promoters contain similar regulatory elements, including an AP-1 site at about -70. There are, however, additional sequences including an adjacent ETS site at about -90 in both promoters, and a NIP (nuclear inhibitory protein) binding site in the stromelysin promoter. In this paper, we have investigated the role of these elements in transcriptional activation by phorbol myristate acetate (PMA). Using mobility shift assays, we demonstrate that in the collagenase promoter, PMA induction requires the binding of nuclear proteins to the ETS site as well as to the adjacent AP-1 element. In the stromelysin promoter, we used mutational analysis and DNA/protein interactions to illustrate a role for a single ETS site and for the NIP element in phorbol induction. These data suggest that ETS elements interact with other cis-acting sequences in these promoters to elicit transcriptional activation, and that the placement of the ETS sites in these promoters may influence transcriptional activity.
White
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Department of Medicine, Dartmouth Medical School, Hanover, NH 03755, USA.
Maute
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Brinckerhoff
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D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D017364:Collagenases / Q000235:genetics*; D006801:Humans; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D011817:Rabbits; D012045:Regulatory Sequences, Nucleic Acid / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; D017364:Collagenases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1; D013755:Tetradecanoylphorbol Acetate