TY - JOUR
T1 - Translational autoregulation of thymidylate synthase and dihydrofolate reductase.
AU - Tai, Ningwen
AU - Schmitz, John C.
AU - Liu, Jun
AU - Lin, Xiukun
AU - Bailly, Michelle
AU - Chen, Tian min
AU - Chu, Edward
PY - 2004
Y1 - 2004
N2 - 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.
AB - 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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U2 - 10.2741/1413
DO - 10.2741/1413
M3 - Review article
C2 - 15353304
AN - SCOPUS:20344381944
SN - 2768-6701
VL - 9
SP - 2521
EP - 2526
JO - Frontiers in bioscience : a journal and virtual library
JF - Frontiers in bioscience : a journal and virtual library
ER -