Thymidylate synthase as a translational regulator of cellular gene expression

Jun Liu, John C. Schmitz, Xiukun Lin, Ningwen Tai, Wu Yan, Michael Farrell, Michelle Bailly, Tian Min Chen, Edward Chu

Research output: Contribution to journalReview articlepeer-review

96 Scopus citations

Abstract

Studies from our laboratory have shown that the folate-dependent enzyme, thymidylate synthase (TS), functions as an RNA binding protein. There is evidence that TS, in addition to interacting with its own TS mRNA, forms a ribonucleoprotein complex with a number of other cellular mRNAs, including those corresponding to the p53 tumor suppressor gene and the myc family of transcription factors. Using both in vitro and in vivo model systems, we have demonstrated that the functional consequence of binding of TS protein to its own cognate mRNA, as well as binding of TS to the p53 mRNA, is translational repression. Herein, we review current work on the translational autoregulatory control of TS expression and discuss the molecular elements that are required for the TS protein-TS mRNA interaction. TS may play a critical role in regulating the cell cycle and the process of apoptosis through its regulatory effects on expression of p53 and perhaps other cell cycle related proteins. Finally, the ability of TS to function as a translational regulator may have important consequences with regard to the development of cellular resistance to various anticancer drugs.

Original languageEnglish (US)
Pages (from-to)174-182
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1587
Issue number2-3
DOIs
StatePublished - Jul 18 2002
Externally publishedYes

Keywords

  • Cancer chemotherapy
  • Gene regulation
  • RNA binding protein
  • Thymidylate synthase
  • Translational regulation

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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