Thymidine kinase 1 (TK1) (TK1)

Thymidine kinase 1 (TK1) is a cytosolic enzyme that plays a pivotal role in the pyrimidine salvage pathway by catalyzing the phosphorylation of thymidine to thymidine monophosphate (dTMP) [UniProt: P04183]. Unlike its mitochondrial counterpart (TK2), TK1 expression is strictly regulated by the cell cycle, with levels rising sharply during the S-phase to facilitate DNA replication [PubMed: 29153355]. This characteristic makes TK1 a highly specific marker for cellular proliferation, particularly in malignant tissues where the enzyme is often overexpressed to meet the high metabolic demands of rapid division. In clinical oncology, TK1 serves as both a diagnostic biomarker and a therapeutic target. Elevated levels of TK1 in the serum are used to monitor tumor aggressiveness, predict recurrence, and evaluate treatment efficacy across various cancers [PubMed: 30264301]. Furthermore, TK1 is the primary enzyme responsible for the intracellular activation of several nucleoside analog drugs, such as trifluridine, which are converted into toxic metabolites that disrupt DNA synthesis and induce apoptosis in cancer cells [DrugBank: DB00432].

Other names

TK-1Cytosolic thymidine kinaseSoluble thymidine kinaseThymidine kinase, cytosolic

Thymidine kinase 1 catalyzes the ATP-dependent phosphorylation of thymidine to thymidine monophosphate (dTMP), providing a critical precursor for DNA synthesis via the salvage pathway [NCBI: Gene ID 7083]. In the context of cancer therapy, it acts by phosphorylating nucleoside analogs (e.g., trifluridine) into their active monophosphate forms, which subsequently interfere with DNA replication and repair [DrugBank: DB00432].