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Negative regulation of the rat stromelysin gene promoter by retinoic acid is mediated by an AP1 binding site.

1990; Springer Nature; Volume: 9; Issue: 13 Linguagem: Inglês

10.1002/j.1460-2075.1990.tb07895.x

1460-2075

R. C. Nicholson, Sylvie Mader, Sunil Nagpal, Mark Leid, Cécile Rochette‐Egly, Pierre Chambon,

Protein Degradation and Inhibitors

Research Article1 December 1990free access Negative regulation of the rat stromelysin gene promoter by retinoic acid is mediated by an AP1 binding site. R. C. Nicholson R. C. Nicholson Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France. Search for more papers by this author S. Mader S. Mader Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France. Search for more papers by this author S. Nagpal S. Nagpal Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France. Search for more papers by this author M. Leid M. Leid Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France. Search for more papers by this author C. Rochette-Egly C. Rochette-Egly Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France. Search for more papers by this author P. Chambon P. Chambon Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France. Search for more papers by this author R. C. Nicholson R. C. Nicholson Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France. Search for more papers by this author S. Mader S. Mader Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France. Search for more papers by this author S. Nagpal S. Nagpal Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France. Search for more papers by this author M. Leid M. Leid Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France. Search for more papers by this author C. Rochette-Egly C. Rochette-Egly Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France. Search for more papers by this author P. Chambon P. Chambon Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France. Search for more papers by this author Author Information R. C. Nicholson1, S. Mader1, S. Nagpal1, M. Leid1, C. Rochette-Egly1 and P. Chambon1 1Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France. The EMBO Journal (1990)9:4443-4454https://doi.org/10.1002/j.1460-2075.1990.tb07895.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Stromelysin is a member of the metalloproteinase family which plays an important role in extracellular matrix remodelling during many normal and disease processes. We show here that in polyomavirus-transformed rat embryo fibroblast cells (PyT21), the transcription from the stromelysin gene is repressed by the vitamin A derivative retinoic acid (RA). Furthermore, expression vectors encoding the human RA receptors hRAR-alpha, hRAR-beta and hRAR-gamma repress chloramphenicol acetyltransferase (CAT) expression from stromelysin promoter-CAT gene expression vectors in RA-treated PyT21 and human HeLa cells, as determined by transient transfection assays. Through mutation and deletion analysis, we show that the RA dependent repression is mediated by a 25 bp region from nucleotide positions -72 to -48 of the rat stromelysin 5′-flanking DNA sequence. Further mutation analysis of this region indicates that the DNA sequence required for RA dependent repression colocalizes with an AP1 binding site which is essential for promoter activity. We show also that RA represses the transcriptional activity of a reporter gene containing a TPA responding AP1 binding site driving the HSV tk promoter. Thus the RAR-RA complex appears to repress transcription of the stromelysin gene by blocking activation by positive regulatory factors. However, we found no evidence supporting the possibility that the RA dependent repression could be due to RAR binding to the AP1 binding site or to the AP1 components c-fos and c-jun. Previous ArticleNext Article Volume 9Issue 131 December 1990In this issue RelatedDetailsLoading ...