title: Functional significance of a putative sp1 transcription factor binding site in the survivin gene promoter.
abstract: We sequenced 1500-bp genomic DNA regions upstream from the survivin gene (BIRC5). DNA was isolated from human placenta and tumors of patients with diagnosed squamous cancer of the lung that showed high-level BIRC5 gene expression. We have revealed four new promoter allelic variants differing in single nucleotide substitutions, one variant with two nucleotide substitutions, and a variant with a TAAA tetranucleotide insertion. All promoter variants displayed low activity in cells with functionally active p53 protein and high activity in cell lines characterized by low level or absence of p53 protein function. The activity of the promoters with single nucleotide substitutions was comparable to that of the wild-type promoter, whereas two nucleotide substitutions markedly reduced the activity. We also demonstrated the functional significance of a putative Sp1 transcription factor-binding site at (-63...-54) upstream from the transcription initiation site. Mutation within this sequence led to a sharp decrease of promoter activity. The functional architecture of the survivin promoter is discussed based on results known from the literature and those obtained here.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia. mityaev@humgen.siobc.ras.ru
authors.forename: M V
authors.initials: MV
authors.lastname: Mityaev
authors.forename: E P
authors.initials: EP
authors.lastname: Kopantzev
authors.forename: A A
authors.initials: AA
authors.lastname: Buzdin
authors.forename: T V
authors.initials: TV
authors.lastname: Vinogradova
authors.forename: E D
authors.initials: ED
authors.lastname: Sverdlov
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D017930:Genes, Reporter; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D000077022:Survivin; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D016329:Sp1 Transcription Factor; D000077022:Survivin