Open Access
Translational autoregulation of thymidylate synthase and dihydrofolate reductase
Ningwen Tai1,John C Schmitz1,Jun Liu1,Xiukun Lin1,Michelle Bailly1,Tian-min Chen1,Edward Chu1
Department of Medicine and Pharmacology, Yale Cancer Center, Yale University School of Medicine and VACT Healthcare System, New Haven, CT 06516, USA
DOI: 10.2741/1413 Volume 9 Issue 4, pp.2521-2526
Published: 01 September 2004
(This article belongs to the Special Issue Thymidylate synthase in biology and cancer treatment)

The folate-dependent enzymes, thymidylate synthase (TS) and dihydrofolate reductase (DHFR) are critical for providing the requisite nucleotide precursors for maintaining DNA synthesis and DNA repair. In addition to their essential roles in enzyme catalysis, these two enzymes have now been shown to function as RNA binding proteins. Using in vitro and in vivo experimental model systems, we have shown that the functional consequence of binding of TS protein to its own cognate mRNA, as well as binding of DHFR to its own DHFR mRNA, is translational repression. Herein, we review and update studies focusing on the translational autoregulatory control of TS and DHFR expression and discuss the molecular elements that are required for these specific RNA-protein interactions. Moreover, we present evidence showing that abrogation of these normal translational autoregulatory feedback mechanisms provides the molecular basis for the rapid development of cellular drug resistance.

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Ningwen Tai, John C Schmitz, Jun Liu, Xiukun Lin, Michelle Bailly, Tian-min Chen, Edward Chu. Translational autoregulation of thymidylate synthase and dihydrofolate reductase. Frontiers in Bioscience-Landmark. 2004. 9(4); 2521-2526.