2010
DOI: 10.1016/j.ejmech.2009.11.054
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Abstract: Aberrant regulation of cap-dependent translation has been frequently observed in the development of cancer. Association of the cap binding protein eIF4E with N 7 -methylated guanosine capped mRNA is the rate limiting step governing translation initiation; and therefore represents an attractive process for cancer drug discovery. Previously, replacement of the 7-Me group of the Me 7 -guanosine monophosphate with a benzyl group has been found to increase binding affinity to eIF4E. Recent Xray crystallographic stu… Show more

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Cited by 41 publications
(44 citation statements)
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“…Mutation of the cap-binding site of eIF4E impairs its activities in translation, mRNA export, and oncogenic transformation (12). Targeting the eIF4E-cap complex with a competitive m 7 G cap inhibitor is a promising strategy to generate anticancer agents (13,14). One such inhibitor, ribavirin, has reached clinical trials where it was used in poor-prognosis leukemia patients.…”
mentioning
confidence: 99%
“…Mutation of the cap-binding site of eIF4E impairs its activities in translation, mRNA export, and oncogenic transformation (12). Targeting the eIF4E-cap complex with a competitive m 7 G cap inhibitor is a promising strategy to generate anticancer agents (13,14). One such inhibitor, ribavirin, has reached clinical trials where it was used in poor-prognosis leukemia patients.…”
mentioning
confidence: 99%
“…Extensive work has been done establishing eIF4E as an oncogene; hence, different strategies are being employed to target eIF4E either directly through the use of ASOs 27 or through the use of small-molecule inhibitors, which inhibit either the eIF4E-eIF4G interaction [19][20][21] or the eIF4E to mRNA cap association 23,25 or target eIF4E indirectly like mTOR inhibitors, 31 which repress the downstream phosphorylation of 4E-BP1 and make eIF4E unavailable for initiation of translation. In the present study, we show that eIF4E levels were significantly reduced in a dose-dependent manner in NSCLC cells treated with 4EASO.…”
Section: Discussionmentioning
confidence: 99%
“…When breast carcinoma cancer cell lines were treated with 4Ei1 combined with the drug 5-fluorouracil there was enhanced cytostatic and/or cytotoxic effects compared with each compound alone. 25 One tactic that was employed to decrease eIF4E abundance in breast carcinoma subtypes was with treatments that used short-interfering RNA against eIF4E. 26 eIF4E knockdown led to growth inhibition of breast cancer cell lines and also decreased the expression of the oncogenic proteins, Cyclin D1, Bcl-2 and Bcl-xL.…”
Section: Introductionmentioning
confidence: 99%
“…Binding protein eIF4E to N(7)-methylated guanosine capped mRNA has been found to be the rate-limiting step governing translation initiation, and therefore represents an attractive target for drug discovery. It has been found that 7-benzyl guanosine monophosphate (7Bn-GMP) is a potent antagonist of (19,20). Recent X-ray crystallographic studies have revealed that the capdependent pocket undergoes a unique structural change in order to accommodate the benzyl group.…”
Section: Disruptors Of 5' Cap Complexmentioning
confidence: 99%