tk1

Thymidine kinase 1 (TK1) is a cytosolic enzyme that participates in the deoxyribonucleoside salvage pathway, catalyzing the phosphorylation of thymidine to thymidine monophosphate (dTMP) using ATP. By supplying dTMP, TK1 helps replenish the deoxynucleotide triphosphate pools required for DNA synthesis, particularly during cell proliferation. In humans, TK1 typically forms a functional homotetramer and is active mainly in the S phase of the cell cycle.

The expression and activity of TK1 are tightly linked to cell cycle control. TK1 levels rise during the G1/S transition and peak in S phase before declining as cells progress through the cycle or differentiate. In nondividing or quiescent cells, TK1 expression is markedly reduced. Transcriptional regulation involves cell cycle–related factors such as E2F, and the protein is also subject to degradation outside of S phase, ensuring it aligns with DNA replication needs.

Clinically, TK1 has been studied as a proliferation marker in oncology. Increased TK1 activity or TK1 protein levels are observed in a range of cancers and correlate with tumor burden and response to therapy in many cases. Measurements can be made in tumor tissue or non-invasively in serum, where serum TK1 (sTK1) activity or concentration has been explored as a biomarker for monitoring disease progression and treatment effectiveness.

TK1 is distinct from thymidine kinase 2 (TK2) and viral thymidine kinases, as TK1 is cytosolic and primarily associated with proliferating cells, whereas TK2 is mitochondrial and more constitutive. TK1 remains a focus of research for understanding DNA synthesis regulation and for developing proliferation-based diagnostics.