Translational autoregulation of thymidylate synthase and dihydrofolate reductase.

Ningwen Tai, John C. Schmitz, Jun Liu, Xiukun Lin, Michelle Bailly, Tian min Chen, Edward Chu

Research output: Contribution to journalReview articlepeer-review

45 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2521-2526
Number of pages6
JournalFrontiers in bioscience : a journal and virtual library
Volume9
DOIs
StatePublished - Sep 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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