Accelerated Publication

Biochemistry (Moscow)

, Volume 73, Issue 11, pp 1183-1191

First online:

Functional significance of a putative Sp1 transcription factor binding site in the survivin gene promoter

  • M. V. MityaevAffiliated withShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences Email author 
  • , E. P. KopantzevAffiliated withShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
  • , A. A. BuzdinAffiliated withShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
  • , T. V. VinogradovaAffiliated withShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
  • , E. D. SverdlovAffiliated withShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences

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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.

Key words

survivin promoter regulation of promoter activity Sp1 binding sites SNP