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1995-05-31 - Article/Dans un journal avec peer-review - Anglais - 9 page(s)

Bulens Franck, Ibañez-Tallon I, Van Acker Petra, De Vriese Astrid, Nelles L, Belayew Alexandra , Collen Désiré, "Retinoic acid induction of human tissue-type plasminogen activator (t-PA) gene expression via a direct repeat element (DR5) located at -7 kb" in International Journal of Biological Chemistry, 270

  • Edition : Asian Network for Scientific Information
  • Codes CREF : Biologie moléculaire (DI3111), Acides nucléiques, synthèse des protéines (DI311A)
  • Unités de recherche UMONS : Biologie moléculaire (M122)
Texte intégral :

Abstract(s) :

(Anglais) All-trans-retinoic acid (RA) and retinoids induce synthesis of tissue-type plasminogen activator (t-PA) in endothelial and neuroblastoma cells in vitro and in rats in vivo. In HT1080 fibrosarcoma cells, induction of t-PA-related antigen secretion and t-PA mRNA steady state levels by RA were found to depend on de novo protein and mRNA synthesis. Fragments derived from the 5'-flanking region of the t-PA gene (+197 to -9578 base pairs (bp)) were linked to the chloramphenicol acetyltransferase gene. Transfection studies demonstrated that the region spanning bp -7145 to -9578 mediated induction by RA. A functional retinoic acid response element (RARE), consisting of a direct repeat of the GGGTCA motif spaced by 5 nucleotides (t-PA/DR5), was localized at -7.3 kilobases. The t-PA/DR5 element interacted with the heterodimer composed of retinoic acid receptor a and retinoid X receptor a in vitro, whereas its mutation abolished induction by RA in transient expression. In human EA.hy926 hybrid endothelial and in SK-N-SH neuroblastoma cells, the activity of t-PA/DR5 was found to be independent of the intervening sequence (-632 to -7144 bp) and of its distance from the transcription initiation site. Staurosporine, an inhibitor of protein kinase activity, inhibited induction by RA, suggesting that it required protein phosphorylation.