ArticleProceedings of the National Academy of Sciences of the United States of America2014
Structure of the eukaryotic translation initiation factor eIF4E in complex with 4EGI-1 reveals an allosteric mechanism for dissociating eIF4G.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
53 citing papers in PubMed, 90 citations in OpenAlex.
- Trial
- Disruption of HSPA8-GEMIN5 interaction suppresses colorectal cancer by impaired splicing-translation coupling-mediated proteostasis imbalance.Journal of experimental & clinical cancer research : CR · 2026Article
- Review
- Two eIF4E paralogs occupy separate germ granule messenger ribonucleoproteins that mediate mRNA repression and translational activation.Genetics · 2025Article
- Chemical Probes for Studying the Eukaryotic Translation Initiation Factor 4E (eIF4E)-Regulated Translatome in Cancer.ACS pharmacology & translational science · 2025Review
- Eukaryotic initiation factors: central factor associating mRNA translational plasticity during neuropathic pain progression.Frontiers in neurology · 2025Review
- Biochemical analysis of human eIF4E-DCP2 interaction: Implications for the relationship between translation initiation and decapping.PloS one · 2025Article
- eIF4E orchestrates mRNA processing, RNA export and translation to modify specific protein production.Nucleus (Austin, Tex.) · 2024Review
- Integrating fragment-based screening with targeted protein degradation and genetic rescue to explore eIF4E function.Nature communications · 2024Article
- Synthesis of Alkyl/Aryloxymethyl Derivatives of 1,2,4-Triazole-3-Carboxamides and Their Biological Activities.Molecules (Basel, Switzerland) · 2024Article
- Structural analysis of the Trypanosoma brucei EIF4E6/EIF4G5 complex reveals details of the interaction between unusual eIF4F subunits.Scientific reports · 2024Article
- Design of Cell-Permeable Inhibitors of Eukaryotic Translation Initiation Factor 4E (eIF4E) for Inhibiting Aberrant Cap-Dependent Translation in Cancer.Journal of medicinal chemistry · 2023Article
- Relationship between SugarcanePlants (Basel, Switzerland) · 2023Article
- Medicinal chemistry approaches to target the MNK-eIF4E axis in cancer.RSC medicinal chemistry · 2023Review
- Design of Cell-Permeable Inhibitors of Eukaryotic Translation Initiation Factor 4E (eIF4E) for Inhibiting Aberrant Cap-Dependent Translation in Cancer.bioRxiv : the preprint server for biology · 2023Article
- The eIF4EBP-eIF4E axis regulates CD4iScience · 2023Article
- Review
- Cancer cells hijack RNA processing to rewrite the message.Biochemical Society transactions · 2022Article
- The metaphorical swiss army knife: The multitude and diverse roles of HEAT domains in eukaryotic translation initiation.Nucleic acids research · 2022Review
- Control of the eIF4E activity: structural insights and pharmacological implications.Cellular and molecular life sciences : CMLS · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
The interaction of the eukaryotic translation initiation factor eIF4E with the initiation factor eIF4G recruits the 40S ribosomal particle to the 5' end of mRNAs, facilitates scanning to the AUG start codon, and is crucial for eukaryotic translation of nearly all genes. Efficient recruitment of the 40S particle is particularly important for translation of mRNAs encoding oncoproteins and growth-promoting factors, which often harbor complex 5' UTRs and require efficient initiation. Thus, inhibiting the eIF4E/eIF4G interaction has emerged as a previously unpursued route for developing anticancer agents. Indeed, we discovered small-molecule inhibitors of this eIF4E/eIF4G interaction (4EGIs) that inhibit translation initiation both in vitro and in vivo and were used successfully in numerous cancer-biology and neurobiology studies. However, their detailed molecular mechanism of action has remained elusive. Here, we show that the eIF4E/eIF4G inhibitor 4EGI-1 acts allosterically by binding to a site on eIF4E distant from the eIF4G binding epitope. Data from NMR mapping and high-resolution crystal structures are congruent with this mechanism, where 4EGI-1 attaches to a hydrophobic pocket of eIF4E between β-sheet2 (L60-T68) and α-helix1 (E69-N77), causing localized conformational changes mainly in the H78-L85 region. It acts by unfolding a short 310-helix (S82-L85) while extending α-helix1 by one turn (H78-S82). This unusual helix rearrangement has not been seen in any previous eIF4E structure and reveals elements of an allosteric inhibition mechanism leading to the dislocation of eIF4G from eIF4E.
Indexed as
Identifiers
What OpenQuestion holds
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.