Genomic structure, chromosomal mapping, and promoter region analysis of murine uridine phosphorylase gene. Academic Article uri icon

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.

published proceedings

  • Cancer Res

author list (cited authors)

  • Cao, D., Nimmakayalu, M. A., Wang, F., Zhang, D., Handschumacher, R. E., Bray-Ward, P., & Pizzorno, G

citation count

  • 5

complete list of authors

  • Cao, D||Nimmakayalu, MA||Wang, F||Zhang, D||Handschumacher, RE||Bray-Ward, P||Pizzorno, G

publication date

  • October 1999