Genomic structure, chromosomal mapping, and promoter region analysis of murine uridine phosphorylase gene. | Academic Article individual record
abstract

Uridine phosphorylase (UPase) plays an important role in the activation of 5-fluorouracil and in the regulation of tissue and plasma concentration of uridine, a potential biochemical modulator of 5-fluorouracil therapy. UPase expression is affected by the c-H-ras oncogene and various cytokines through unknown mechanisms. To understand its expression and regulation, we cloned the murine UPase gene, defined its genomic organization, determined its 5'- and 3'-end flanking sequences, and evaluated the promoter activity. The UPase gene contains nine exons and eight introns, spanning a total of approximately 18.0 kb. Its promoter lacks canonical TATA and CCAAT boxes, although a CAATAAAAA TATA-like box is seen from -41 to -49. Furthermore, IFN regulatory factor 1, c/v-Myb, and p53 binding sites are present in the promoter region, indicating that UPase expression may be directly regulated by cytokines and oncogene products. The 1.2-kb flanking fragment showed promoter activity driving the expression of the luciferase gene in various mammalian cells. A TGGGG repeat sequence is seen in the 3'-end flanking region. This element is considered to be a potential recombination consensus hot spot that may contribute to the encoding of different UPase isoforms present in different tissues, both normal and neoplastic.

authors
author list (cited authors)
Cao, D., Nimmakayalu, M. A., Wang, F., Zhang, D., Handschumacher, R. E., Bray-Ward, P., & Pizzorno, G.
publication date
1999
published in
keywords
  • 5' Untranslated Regions
  • Lymphocytes
  • Exons
  • DNA-Binding Proteins
  • Chromosome Mapping
  • Molecular Sequence Data
  • Binding Sites
  • Mice
  • Animals
  • Restriction Mapping
  • Base Sequence
  • Promoter Regions, Genetic
  • 3' Untranslated Regions
  • Introns
  • Cloning, Molecular
  • Gene Expression Regulation, Enzymologic
  • Spleen
  • Uridine Phosphorylase
  • Karyotyping
  • Polymerase Chain Reaction
citation count

4