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.
