Transcriptional control of SPARC by v-Jun and other members of the AP1 family of transcription factors.
Transformation of chick embryo fibroblasts by the v-Jun oncoprotein correlates with a down-regulation of the extracellular matrix protein SPARC and repression of the corresponding mRNA. Alteration in SPARC expression has been repeatedly reported in human cancers of various origin, and is thought to contribute to the remodeling of the extracellular matrix during neoplastic progression. Transcriptional control of SPARC is poorly understood. We show here that (i) v-Jun-mediated repression of the endogenous SPARC gene is enhanced by Fra2 but alleviated by ATF2, Fra2 and ATF2 being the two major partners of v-Jun in the transformed cells; (ii) high basal activity as well as repression by v-Jun and modulation by Fra2 and ATF2 is restricted to a small proximal fragment (-124/+16) of the chicken SPARC promoter; (iii) the activity of this minimal promoter is modulated by all the AP1 family members known in chickens (c-Jun and JunD; c-Fos and Fra2; ATF2; c-Maf, MafA, and MafB). Taken together these data demonstrate that, at least in avian primary cells, SPARC expression is under the control of the AP1 transcription factor. Further studies with the minimal (-124/+16) promoter fragment are needed to understand how this control takes place at the molecular level.
Vial
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Unité de Virologie Humaine, Institut National de la Santé et de la Recherche Médicale (INSERM-U412), Ecole Normale Supérieure, 46 allée d'Italie, 69364 Lyon Cedex 07, France.
Perez
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Castellazzi
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D051698:Activating Transcription Factor 2; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002642:Chick Embryo; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D051921:Fos-Related Antigen-2; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016759:Oncogene Protein p65(gag-jun) / Q000235:genetics / Q000502:physiology*; D015676:Osteonectin / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D051257:Proto-Oncogene Proteins c-maf; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C497872:FOSL2 protein, human; D051921:Fos-Related Antigen-2; C497873:Fosl2 protein, mouse; C495607:MAF protein, human; C495608:Maf protein, mouse; D016759:Oncogene Protein p65(gag-jun); D015676:Osteonectin; D011518:Proto-Oncogene Proteins; D051257:Proto-Oncogene Proteins c-maf; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors