Cytidine monophosphate kinase 1 (CMPK1)

Cytidine monophosphate kinase 1 (CMPK1) is a cytosolic enzyme that plays a pivotal role in the pyrimidine nucleotide biosynthetic and salvage pathways by catalyzing the ATP-dependent phosphorylation of CMP, UMP, and dCMP into their respective diphosphate forms [1, 6]. This enzymatic activity is essential for maintaining the cellular pools of nucleotides required for DNA and RNA synthesis, as well as DNA repair processes [2, 3]. In clinical medicine, CMPK1 is a critical determinant of the efficacy of several pyrimidine-based nucleoside analog prodrugs, such as gemcitabine, cytarabine, and 5-fluorouracil, as it performs the necessary second step of their metabolic activation [2, 9]. Low expression or downregulation of CMPK1, often mediated by microRNAs like miR-130b, is a significant mechanism of chemoresistance in various cancers, including gastric and pancreatic cancer [9]. Furthermore, CMPK1 has been identified as a binding target for doxorubicin, suggesting a role in anthracycline-mediated effects and toxicity [5]. Recent studies also highlight its potential as a biomarker and therapeutic target in non-oncological conditions such as type 2 diabetes and acute kidney injury [11, 12].

Other names

UMP-CMP kinaseUMP/CMP kinaseCytidylate kinasedCMP kinaseDeoxycytidylate kinaseUridine monophosphate kinaseKCY

CMPK1 facilitates the activation of pyrimidine nucleoside analog prodrugs by catalyzing the phosphorylation of their monophosphate forms into diphosphates [2, 9]. It also serves as a binding target for doxorubicin, which can upregulate its activity and potentially influence drug-induced toxicity [5].