ArticleBiochemical and biophysical research communications2013
Conformational changes induced in the eukaryotic translation initiation factor eIF4E by a clinically relevant inhibitor, ribavirin triphosphate.
Article in Biochemical and biophysical research communications, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Trial
- eIF4E and Ezrin cooperate in pseudopods to drive a localized migratory translation program in acute myeloid leukemia.bioRxiv : the preprint server for biology · 2026Article
- Multipurpose RNA maturation factors dysregulate multiple mRNA processing steps simultaneously and provide new therapeutic opportunities.RNA biology · 2025Review
- Review
- The eukaryotic translation initiation factor eIF4E unexpectedly acts in splicing thereby coupling mRNA processing with translation: eIF4E induces widescale splicing reprogramming providing system-wide connectivity between splicing, nuclear mRNA export and translation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024Article
- N7-methylguanosine modification: from regulatory roles to therapeutic implications in cancer.American journal of cancer research · 2023Review
- Cancer cells hijack RNA processing to rewrite the message.Biochemical Society transactions · 2022Article
- Review
- The Nuclear Pore Complex and mRNA Export in Cancer.Cancers · 2020Review
- The diversity, plasticity, and adaptability of cap-dependent translation initiation and the associated machinery.RNA biology · 2020Review
- Article
- The Impact of Post-transcriptional Control: Better Living Through RNA Regulons.Frontiers in genetics · 2018Review
- Article
- Metabolism, Biochemical Actions, and Chemical Synthesis of Anticancer Nucleosides, Nucleotides, and Base Analogs.Chemical reviews · 2016Review
- Importin 8 mediates m7G cap-sensitive nuclear import of the eukaryotic translation initiation factor eIF4E.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- The eukaryotic translation initiation factor eIF4E wears a "cap" for many occasions.Translation (Austin, Tex.) · 2016Article
- The eukaryotic translation initiation factor eIF4E in the nucleus: taking the road less traveled.Immunological reviews · 2015Review
- Article
- When will resistance be futile?Cancer research · 2014Review
- Macromolecular transport between the nucleus and the cytoplasm: Advances in mechanism and emerging links to disease.Biochimica et biophysica acta · 2014Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The eukaryotic translation initiation factor eIF4E is highly elevated in human cancers including acute myeloid leukemia (AML). A potential anticancer agent, ribavirin, targets eIF4E activity in AML patients corresponding to clinical responses. To date, ribavirin is the only direct inhibitor of eIF4E to reach clinical trials. We showed that ribavirin acts as a competitive inhibitor of the methyl 7-guanosine (m(7)G) cap, the natural ligand of eIF4E. Here we examine the conformational changes occurring in human eIF4E upon binding the active metabolite of ribavirin, ribavirin triphosphate (RTP). Our NMR data revealed an unexpected concentration dependence on RTP affinity for eIF4E. We observed NMR spectra characteristic of tight binding at low micromolar concentrations (2-5 μM eIF4E) but much weaker affinity at more typical NMR concentrations (50- ). Comparison of chemical shift perturbation and line broadening suggest that the two eIF4E-RTP complexes differ in the precise positioning of RTP within the cap binding pocket, with the high affinity complex showing more extensive changes to the central β-sheet and dorsal surface of eIF4E, similar to m(7)G cap. The differences between high and low affinity complexes arise due to concentration dependent aggregation of eIF4E and RTP. Given the intracellular concentrations of eIF4E and RTP and the differential binding toward the W56A eIF4E mutant the high affinity complex is the most physiologically relevant. In summary, these findings demonstrate that RTP binds in the cap-binding site but also suggests new features of this pocket that should be considered in drug design efforts and reveal new insights into ligand eIF4E recognition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.