title: The role of a single-stranded nucleotide loop in transcriptional regulation of the human sod2 gene.
abstract: Manganese superoxide dismutase (MnSOD), a mitochondrial antioxidant enzyme, is necessary for survival of aerobic life. Previously, we demonstrated that a Sp1-based promoter is essential for constitutive transcription and a NF-kappaB-based intronic enhancer is responsible for cytokine-mediated induction. Here we show that nucleophosmin (NPM), a RNA-binding protein, binds to an 11G single-stranded loop in the promoter region and serves to integrate the Sp1 and NF-kappaB responses. Disruption of the loop structure causes a reduction of both constitutive and inductive transcription due to loss of the binding motif for NPM. Interaction of NF-kappaB.NPM.Sp1 facilitated by binding of NPM to the loop structure in the promoter region appears to comprise the basic complex for the transcriptional stimulation. These results suggest a novel molecular mechanism for communication between the enhancer and the GC-rich promoter.
authors.affiliation: Graduate Center for Toxicology, Department of Radiation Medicine, University of Kentucky, Lexington 40536-0305, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Sanjit K
authors.initials: SK
authors.lastname: Dhar
authors.forename: William H
authors.initials: WH
authors.lastname: St Clair
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Kasarskis
authors.forename: Daret K
authors.initials: DK
authors.lastname: St Clair
mesh_terms: D002461:Cell Line, Transformed; D004277:DNA, Single-Stranded / Q000235:genetics* / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D020862:GC Rich Sequence / Q000502:physiology; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009690:Nucleic Acid Conformation; D000090243:Nucleophosmin; D011485:Protein Binding / Q000502:physiology; D020218:Response Elements / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic / Q000502:physiology*; D000099156:Superoxide Dismutase 2
chemical_list: D004277:DNA, Single-Stranded; D016328:NF-kappa B; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D016329:Sp1 Transcription Factor; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C000716967:NPM1 protein, human