Genomic structure, chromosomal mapping, and promoter region analysis of murine uridine phosphorylase gene

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 throu gh unknown mechanisms. To understand its expression and regulation, we clon ed 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 appr oximately 18.0 kb. Its promoter lacks canonical TATA and CCAAT boxes, altho ugh a CAATAAAAA TATA-like box is seen from -41 to -49. Furthermore, IFN reg ulatory factor 1, c/v-Myb, and p53 binding sites are present in the promote r region, indicating that UPase expression may be directly regulated by cyt okines 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 t hat may contribute to the encoding of different UPase isoforms present in d ifferent tissues, both normal and neoplastic.