Uridine-cytidine kinase 2 (UCK2) (UCK2)

Uridine-cytidine kinase 2 (UCK2) is a rate-limiting enzyme in the pyrimidine salvage pathway, responsible for the phosphorylation of uridine and cytidine into their respective monophosphates (UniProt Q9BZX2). While the protein functions as an activating enzyme for various nucleoside analog prodrugs, UCK2 mRNA is also a direct therapeutic target for RNA-based interventions, such as small interfering RNAs (siRNAs), aimed at reducing its overexpression in malignancies like hepatocellular carcinoma and pancreatic cancer (PMID: 30033434). UCK2 is highly upregulated in tumor tissues compared to normal adult tissues, where its expression is generally low or absent, providing a wide therapeutic window (NCBI Gene 7371). In the context of prodrug therapy, drugs like RX-3117 (fluorocyclopentenylcytosine) require UCK2-mediated phosphorylation to become active cytotoxic agents that inhibit DNA and RNA synthesis (PMID: 27531894). Conversely, silencing UCK2 mRNA has been shown to inhibit cell proliferation and induce apoptosis in cancer cells, highlighting its dual role as both a prodrug activator and an oncogenic driver (PMID: 31510418). Consequently, UCK2 mRNA and protein levels serve as critical biomarkers for predicting patient response to these specific chemotherapeutic agents.

Other names

UCK 2Uridine-cytidine kinase 2Cytidine kinase 2UKEURPUCK2 mRNA

Activation of nucleoside prodrugs via phosphorylation to monophosphate forms; inhibition of pyrimidine metabolism via gene silencing.