Involvement of Sp1 in basal and retinoic acid induced transcription of the human tissue-type plasminogen activator gene.
Transcription of the human tissue-type plasminogen activator (t-PA) gene is regulated by a multi-hormonal responsive enhancer at -7 kb. Transient co-transfections of Drosophila SL2 and human HT1080 fibrosarcoma cells with t-PA reporter constructs showed that Sp1 and Sp3 activate the t-PA promoter. Moreover Sp1 (but not Sp3) binding to the promoter is involved in induction by retinoic acid (RA), a response mediated through the enhancer. The role of Sp1 is specific, since mutation of the CRE element in the promoter did not affect response to RA. In contrast, the glucocorticoid induction mediated by the enhancer is independent of these Sp1 and CRE elements.
Merchiers
P
P
Center for Molecular and Vascular Biology, University of Leuven, Belgium.
Bulens
F
F
De Vriese
A
A
Collen
D
D
Belayew
A
A
D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004330:Drosophila / Q000166:cytology; D005354:Fibrosarcoma / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051705:Sp3 Transcription Factor; D010959:Tissue Plasminogen Activator / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology
D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D051705:Sp3 Transcription Factor; D014212:Tretinoin; D003907:Dexamethasone; D010959:Tissue Plasminogen Activator