Molecular Mechanisms Regulating the Expression of Thymidylate Synthase

Abstract: Thymidylate synthase (TS)， an essential enzyme for catalyzing the biosynthesis of thymidylate， is a critical therapeutic target in cancer therapy. Previous study indicated that the level of gene amplification， transcription， translation， and posttranslation were all involved in regulating the expression of TS. Studies have shown that TS was able to bind to its own mRNA to form TS protein-TS mRNA complex， and this interaction resulted in translational suppression. When TS is bound by 5-fluorouracil (5-FU) or other antimetabolite， the RNA binding activity of TS is dramatically decreased. The effect of reduced RNA binding activity is relief of translational repression， a process that leads to increased synthesis of new TS protein. Thus， this model provides a rational mechanism for the development of drug resistance in tumor cells. In this paper， the mechanisms regulating the expression of TS gene were reviewed， and the ability of TS to function as a translational regulator and the molecular mechanisms of drug resistance were also presented.

CSTR: 32200.14.cjcb.2005.02.0002