Genomic structure, chromosomal mapping, and promoter region analysis of murine uridine phosphorylase gene.
Genomic structure, chromosomal mapping, and promoter region analysis of murine uridine phosphorylase gene.
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发表时间：
1999-10
期刊：
影响因子：
11.2
通讯作者：
D. Cao;M. Nimmakayalu;F. Wang;D. Zhang;R. Handschumacher;P. Bray-Ward;G. Pizzorno
中科院分区：
文献类型：
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作者：
D. Cao;M. Nimmakayalu;F. Wang;D. Zhang;R. Handschumacher;P. Bray-Ward;G. Pizzorno
尿苷磷酸化酶（UPase）在5-氟尿嘧啶的活化和尿苷（5-氟尿嘧啶治疗的潜在生化调节剂）的组织和血浆浓度的调节中起重要作用。UPase表达受c-H-ras癌基因和各种细胞因子的影响，其机制尚不清楚。为了了解其表达和调控，我们克隆了鼠UPase基因，定义了其基因组结构，确定了其5 '端和3'端侧翼序列，并评估了启动子活性。UPase基因包含9个外显子和8个内含子，总长度约为18.0 kb。它的启动子缺乏典型的TATA和CCAAT盒，尽管从-41到-49可以看到CAATAAAAA TATA样盒。此外，IFN调节因子1，c/v-Myb，和p53结合位点存在于启动子区域，表明UPase表达可能直接受细胞因子和癌基因产物的调节。1.2 kb侧翼片段显示启动子活性，驱动荧光素酶基因在各种哺乳动物细胞中的表达。TGGGG重复序列见于3 '端侧翼区。该元件被认为是一个潜在的重组共识热点，可能有助于编码存在于不同组织（正常和肿瘤）中的不同UPase亚型。
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.