EC Number   |
General Information |
Reference |
|---|
    2.7.1.48 | drug target |
1-(3-C-ethynyl-beta-D-ribopentofuranosyl)cytosine (ECyd) is a potent inhibitor of RNA polymerase I and shows anticancer activity to various human solid tumors. ECyd is phosphorylated to 3'-ethynylcytidine 5'-monophosphate by uridine/cytidine kinase 2 (UCK2) and subsequently further to diphosphate and triphosphate (3'-ethyntlcytidine 5'-diphosphate, 3'-ethyntlcytidine 5'-triphosphate). 3'-Ethyntlcytidine 5'-triphosphate is an active metabolite that can inhibit RNA polymerase I competitively. IVS5 + 5 G > A mutation would affect the expression level of the UCK2 transcript and result in decreased sensitivity to ECyd. The UCK2 is a key drug-response predictive marker for innate or acquired resistance to uridine/cytidine-type nucleoside analogs |
758650 |
| 2.7.1.48 | drug target |
inhibition of enzyme (UCK2) induces nucleolar stress, probably by depleting nucleotide biosynthesis, thereby destabilising ribosomal biogenesis and subsequently causing cancer cell arrest and apoptotic cell death induction |
758880 |
| 2.7.1.48 | malfunction |
mutagenesis of Tyr93 in ttCK reveals that the uridine phosphorylation activity is restored only by replacement of Tyr93 with His or Gln |
-, 758717 |
| 2.7.1.48 | malfunction |
mutation H117Y of UCK2 results in a loss of uridine phosphorylation activity of the enzyme |
758717 |
| 2.7.1.48 | malfunction |
overexpression of uridine-cytidine kinase 2 correlates with breast cancer progression and poor prognosis. UCK2, along with other genes involved in the 5-FU anabolic pathway, produces a phenotype of cell sensitivity to 5-FU folxadlowing knockdown |
759533 |
| 2.7.1.48 | malfunction |
probable ribosomal stress condition during inhibition of the UCK2 enzyme, overview. The released and subsequent activation of p53 leads towards apoptosis induction |
758880 |
| 2.7.1.48 | malfunction |
role of a uridine/cytidine kinase 2 mutation in cellular sensitiveness toward 3'-ethynylcytidine (ECyd) treatment of human cancer cells. The splice-site mutation of the UCK2 gene resulting in the IVS5+5 G>A variant affects the expression level of the UCK2 transcript, causing decreased sensitivity to ECyd. The IVS5+5 G>A variant generates an aberrant mRNA transcript, namely, truncated mRNA is produced and normal mRNA levels are markedly decreased in the ECyd-resistant cancer cell line HT1080. Relationship of UCK2 mutations and drug sensitivity with ECyd in several cancer cell lines, overview. Detection of the aberrant mRNA transcript in the ECyd/EUrd-resistant cancer cells with the IVS5 +5 A/A genotype |
758650 |
| 2.7.1.48 | malfunction |
UCK from Thermus thermophilus HB8 loses catalytic activity on uridine due to lack of a substrate binding ability and possesses an unusual amino acid, i.e. tyrosine 93 (Tyr93) at the binding site, whereas histidine (His) is located in the other UCKs. Mutagenesis experiments reveal that a replacement of Tyr93 by His or glutamine (Gln) recovers catalytic activity on uridine |
-, 758922 |
| 2.7.1.48 | metabolism |
the enzyme is responsible for the phosphorylation of uridine and cytidine to their corresponding monophosphate in a salvage pathway of pyrimidine nucleotides biosynthesis |
758880 |
| 2.7.1.48 | metabolism |
UCK2 is feedback inhibited by UTP and CTP to adjust cellular needs and prevent overproduction of the nucleotides. In the course of cancer cell proliferation, these nucleotides are continuously synthesized to sustain protein synthesis. During gene degradation, some NMPs are released and recycled via the salvage pathway by the action of UCK2, thereby facilitating the prevention of energy loss and the waste of valuable precursors. Molecular crosstalks between UCK2 and cell death, the role of ribosomal proteins, MDM2 and p53 in regulation of cell death, and the role of UCK2 in regulation of cell death |
758880 |
