Molecular Mechanisms Regulating the Expression of Thymidylate Synthase

摘要: Thymidylate synthase (TS) is a folate-dependent enzyme that catalyzes the reductive methylation of 2′-deoxyuridine-5′-monophosphate (dUMP) by reduced folate 5,10-methylenetetrahydrofolate (CH2THF) to thymidylate (dTMP) and dihydrofolate (Fig. 1) (1,2). Once synthesized, dTMP then further metabolized intracellularly dTTP triphosphate form, an essential precursor for DNA synthesis. Although can be formed through salvage pathway catalyzed thymidine kinase, TS-catalyzed reaction provides sole intracellular de novo source dTMP. Given its central role in biosynthesis, given inhibition this results immediate cessation cellular proliferation growth, TS represents important target cancer chemotherapy (3,4).