title: Suppression of Smad-1 mRNA expression level by Smad-2 likely control dichotomy of NF-κB and Smads mediated activation.
abstract: The aim of this study was to find out how NF-κB and Smad-mediated signaling influenced the expression of astrogliogenic versus neurogenic markers of brain development in U4C cells which were either enriched (Tg Jak-1) or deprived in Jak-1 molecule (Jak-1 KO). Genetically modified U4C cells were transfected with NF-kB reporter plasmid in order to follow its activation when cells were cotransfected with different combinations of Smads constructs. In wild type cells no significant activation of NF-κB was observed while genetically modified cells exhibited somewhat different pattern of NF-κB activation depending on the Smad constructs combination used. The absence of NF-κB activation in Jak-1 transgenic cells transfected with Smad-1 plus Smad-3 was accompanied by the appearance of apoptotic cells as revealed by DAPI staining. Smad-1 expression was undetectable in Jak-1 transgenic cells and was downregulated in wild type cells upon transfection with Smad-2. The absence of p65 nuclear translocation in Smad-2 transfected cells and the presence of Smad-4 in nucleus of the same cells indicates dichotomy in NF-κB and Smads mediated signaling pathways. The significance of this study is that helps to elucidate the point of collaboration among three different signaling pathways - Jak-1 mediated cytokine signaling, NF-κB and Smads mediated pathways.
authors.affiliation: Department of Molecular Medicine, "Rudjer Bošković" Institute, Bijenička 54, Zagreb, Croatia.
authors.forename: N
authors.initials: N
authors.lastname: Slade
authors.affiliation: Department of Molecular Medicine, "Rudjer Bošković" Institute, Bijenička 54, Zagreb, Croatia.
authors.forename: A
authors.initials: A
authors.lastname: Zorić
authors.affiliation: INSERM U758, IFR 128 Biosciences Lyon-Gerland, Tony Garnier, Lyon, France.
authors.forename: B
authors.initials: B
authors.lastname: Horvat
authors.affiliation: Croatian Institute for Brain Research, Šalata 12, Zagreb, Croatia.
authors.forename: M
authors.initials: M
authors.lastname: Vukšić
authors.affiliation: Croatian Institute for Brain Research, Šalata 12, Zagreb, Croatia.
authors.forename: I
authors.initials: I
authors.lastname: Kostović
authors.affiliation: Department of Physiology and Immunology, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Šalata 12, Zagreb, Croatia. Electronic address: lpoljak@hiim.hr.
authors.forename: L
authors.initials: L
authors.lastname: Poljak
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D053613:Janus Kinase 1 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D021381:Protein Transport; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D051898:Smad1 Protein / Q000235:genetics*; D051899:Smad2 Protein / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D051785:Smad Proteins; D051898:Smad1 Protein; D051899:Smad2 Protein; D053613:Janus Kinase 1
keywords: Jak-1 signaling; NF-κB transcription factor; Smads mediators