Disease relevance of UPP1

• The expression levels of UPase and dThdPase are higher in human solid tumors including breast carcinomas than in normal tissues [1].
• Using a mouse cDNA probe we have identified a human uridine phosphorylase cDNA clone from the cDNA library of a human colorectal tumor cell line, HCT116 [2].
• Uridine phosphorylase is a potential prognostic factor in patients with oral squamous cell carcinoma [3].
• High staining of UPase (defined as > 50% of cells in a tumor biopsy that are positive for UPase) in primary tumors frequently was associated with the presence of metastasis to lymph nodes (P = 0.007 by the Fischer exact test) and with lower overall survival (P = 0.03 by the log-rank test) [3].
• Inhibition of nucleoside transport in murine lymphoma L5178Y cells and human erythrocytes by the uridine phosphorylase inhibitors 5-benzylacyclouridine and 5-benzyloxybenzylacyclouridine [4].

High impact information on UPP1

• Exogenous uridine and cytidine are mostly converted to uracil by uridine phosphorylase and cytidine deaminase in T. foetus prior to incorporation [5].
• Up-regulation of uridine phosphorylase by EWS/FLI1 sensitizes cells to growth inhibition by the pyrimidine analogue, 5'-deoxy-5'fluorouridine, both in tissue culture and in vivo model systems [6].
• Ectopic expression of uridine phosphorylase was able to support anchorage-independent cell growth, indicating that it plays an active role in the oncogenic process [6].
• Expression, characterization, and detection of human uridine phosphorylase and identification of variant uridine phosphorolytic activity in selected human tumors [7].
• The polyclonal antibody used to screen a human liver expression library allowed the isolation of a 1.2-kb clone that contained the entire open reading frame of the human UPase [7].

Chemical compound and disease context of UPP1

• Modulation of uridine phosphorylase gene expression by tumor necrosis factor-alpha enhances the antiproliferative activity of the capecitabine intermediate 5'-deoxy-5-fluorouridine in breast cancer cells [8].
• Inhibition of uridine phosphorylase and thymidine phosphorylase by antisense strategies effectively antagonised 5-FU, abolishing 84% and 79% of its toxicity [9].
• Uridine phosphorylase was purified 1,370-fold from sonicated extracts of Acholeplasma laidlawii by ammonium sulfate precipitation, DEAE-Sephadex column chromatography, hydroxylapatite chromatography, and Sephadex G-200 fractionation [10].
• Modulation of 5-fluorouracil host toxicity by 5-(benzyloxybenzyl)barbituric acid acyclonucleoside, a uridine phosphorylase inhibitor, and 2',3',5'-tri-O-acetyluridine, a prodrug of uridine [11].
• Pyrimidine nucleoside catabolism in Sphingomonas paucimobilis: role of cytidine deaminase and uridine phosphorylase [12].

Biological context of UPP1

• The identification of a novel uridine phosphorylase with broad substrate specificity is important for studies on both nucleoside metabolism as well as for studies on the pharmacological mechanisms of therapeutic pyrimidine nucleoside analogs [13].
• The UPase gene expression levels in tumors of patients who relapsed were significantly higher than in those from patients who did not (p = 0.039) [1].
• Assignment of a gene for uridine phosphorylase to chromosome 7 [14].
• The characterization of the promoter region of UPase has indicated a direct regulation of its expression by the tumor suppressor gene p53 [15].
• In this study, we investigated the effect of tumor necrosis factor-alpha (TNF-alpha) on UPase gene expression and 5'-DFUR antiproliferative activity and elucidated the involved signal transduction pathway [8].

Anatomical context of UPP1

• Approximately 60-70% of the total UPase exists in the cytosol as a soluble protein [16].
• Affinity chromatography was utilized to purify UPase from colon 26 and NIH 3T3 cells using the uridine phosphorylase inhibitor 5'-amino benzylacyclouridine linked to an agarose matrix [16].
• Uridine phosphorylase (UPase), a key enzyme in the pyrimidine salvage pathway, is associated with the intermediate filament protein vimentin, in NIH 3T3 fibroblasts and colon 26 cells [16].
• RPL38, FOSL1, and UPP1 are predominantly expressed in the pancreatic ductal epithelium [17].
• Although the expression level of the dThdPase gene was correlated with angiogenesis, detected by immunostaining endothelial cells (R = 0.66), that of UPase gene was not (R = 0.044) [1].

Associations of UPP1 with chemical compounds

• Uridine phosphorylase catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate [13].
• Although the expression levels of neither UPase or dThdPase were associated with age, pT, pN, pM, estrogen or progesterone receptor positivity, the patients with the higher levels of UPase gene expression had worse survival (p = 0.0038) than those with lower levels [1].
• The role of thymidine phosphorylase and uridine phosphorylase in (fluoro)pyrimidine metabolism in peripheral blood mononuclear cells [18].
• The recombinant human uridine phosphorylase expressed in COS-7 cells demonstrated specific enzyme activity with uridine as the substrate; this activity was inhibited by the competitive inhibitor 2,2'-anhydro-5-ethyluridine [2].
• BACKGROUND: Uridine phosphorylase (UPase) catalyzes the reversible phosphorolysis of uridine to uracil [3].

Physical interactions of UPP1

• Transient transfection analysis showed that the TNF-alpha-inductive pattern in EMT6 cells was consistent with the presence of a nuclear factor-kappaB (NF-kappaB) binding element (-1332/-1312 bp) in the UPase promoter region [8].

Regulatory relationships of UPP1

• Our data indicate that TNF-alpha significantly induced UPase mRNA expression and its enzymatic activity in EMT6 murine breast cancer cells, leading to an enhanced cytotoxicity of 5'-DFUR [8].

Other interactions of UPP1

• Our data demonstrate that UPase is associated with both the soluble and insoluble pools of vimentin [16].
• UPP1 has a homology with selenocysteine lyase [19].
• We demonstrate for the first time that UPase is associated with vimentin and the existence of an enzymatically active cytoskeleton-associated UPase [16].
• Thymidine phosphorylase (TP) and uridine phosphorylase (UP) are often upregulated in solid tumors and catalyze the phosphorolysis of natural (deoxy)nucleosides and a wide variety of fluorinated pyrimidine nucleosides [20].
• Results: OPRT, thymidylate synthase, RNR, thymidine phosphorylase, uridine phosphorylase and thymidine kinase activities were significantly higher in tumor areas than in nontumor areas [21].

Analytical, diagnostic and therapeutic context of UPP1

• Vimentin copurification with UPase was confirmed using both Western blot analysis and MALDI-MS methods [16].
• Separation of cytosolic proteins using gel filtration chromatography yields a high molecular weight complex containing UPase and vimentin [16].
• To clarify the correlation between the expression levels of UPase and dThdPase genes and the clinicopathological factors, mRNA levels of these enzymes were examined by RT-PCR in 43 breast carcinomas [1].
• Chromatin immunoprecipitation assays reveal that EWS/FLI1 directly associates with the uridine phosphorylase promoter in vivo [6].
• Furthermore, electrophoretic mobility shift assays, supershift, and cotransfection assays revealed that the activation of p65 was responsible for UPase induction by TNF-alpha [8].

References