Uracil phosphoribosyltransferase (UPRT) (UPRT)

Uracil phosphoribosyltransferase (UPRT) is a key enzyme in the pyrimidine salvage pathway that catalyzes the conversion of uracil and 5-phosphoribosyl-1-pyrophosphate (PRPP) into uracil monophosphate (UMP) [1][2]. In the context of CDUPRT-engineered Mesenchymal Stem Cells (MSCs), UPRT is typically expressed as part of a bifunctional fusion protein with Cytosine Deaminase (CD) to act as a suicide gene therapy system [3]. The CD component converts the non-toxic prodrug 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU), which UPRT then converts directly into 5-fluorouridine monophosphate (5-FUMP), bypassing rate-limiting steps and enhancing the production of cytotoxic metabolites like 5-FdUMP [1][4]. This localized conversion within the tumor microenvironment, facilitated by the natural tumor-homing ability of MSCs, significantly increases the sensitivity of cancer cells to chemotherapy while reducing systemic side effects [3][5]. The primary therapeutic mechanism involves the inhibition of thymidylate synthase and the incorporation of fraudulent nucleotides into RNA and DNA, leading to cell cycle arrest and apoptosis [2][4]. Sources: [1] UniProt (P0A8G6 - UPRT_ECOLI) [2] PubChem (Compound Summary for CID 3385, 5-Fluorouracil) [3] Kucerova, L., et al. (2007). "Cytosine deaminase-expressing human mesenchymal stem cells mediate antitumor effect in a rat glioma model." Cancer Research. [4] Longley, D. B., et al. (2003). "5-fluorouracil: mechanisms of action and clinical strategies." Nature Reviews Cancer. [5] You, M. H., et al. (2009). "Cytotoxic effect of mesenchymal stem cells engineered to express a fusion gene of cytosine deaminase and uracil phosphoribosyltransferase on thyroid cancer cells." Endocrine-Related Cancer.

Other names

UPPFUR1Uracil phosphoribosyltransferaseCD-UPRT fusion proteinCytosine deaminase-uracil phosphoribosyltransferase

Catalyzes the conversion of 5-fluorouracil (5-FU) to 5-fluorouridine monophosphate (5-FUMP), which is further metabolized to inhibitors of thymidylate synthase, thereby disrupting DNA synthesis and inducing apoptosis.