ArticleJournal of virology2011
Noncytotoxic inhibition of viral infection through eIF4F-independent suppression of translation by 4EGi-1.
Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- High-throughput translational profiling with riboPLATE-seq.Scientific reports · 2022Article
- Inhibition of coronavirus HCoV-OC43 by targeting the eIF4F complex.Frontiers in pharmacology · 2022Article
- The Food and Drug Administration-approved antipsychotic drug trifluoperazine, a calmodulin antagonist, inhibits viral replication through PERK-eIF2α axis.Frontiers in microbiology · 2022Article
- A biphenyl inhibitor of eIF4E targeting an internal binding site enables the design of cell-permeable PROTAC-degraders.European journal of medicinal chemistry · 2021Article
- Gene- and Species-Specific Hox mRNA Translation by Ribosome Expansion Segments.Molecular cell · 2020Article
- The diversity, plasticity, and adaptability of cap-dependent translation initiation and the associated machinery.RNA biology · 2020Review
- mTOR Dysregulation by Vaccinia Virus F17 Controls Multiple Processes with Varying Roles in Infection.Journal of virology · 2019Article
- RACK1 evolved species-specific multifunctionality in translational control through sequence plasticity within a loop domain.Journal of cell science · 2019Article
- Consideration of Binding Kinetics in the Design of Stapled Peptide Mimics of the Disordered Proteins Eukaryotic Translation Initiation Factor 4E-Binding Protein 1 and Eukaryotic Translation Initiation Factor 4G.Journal of medicinal chemistry · 2019Article
- Translational control during poxvirus infection.Wiley interdisciplinary reviews. RNA · 2019Review
- Therapeutic Opportunities in Eukaryotic Translation.Cold Spring Harbor perspectives in biology · 2018Review
- Translation initiation mediated by nuclear cap-binding protein complex.BMB reports · 2017Review
- Stress Beyond Translation: Poxviruses and More.Viruses · 2016Review
- Murine norovirus 1 (MNV1) replication induces translational control of the host by regulating eIF4E activity during infection.The Journal of biological chemistry · 2015Article
- The synergistic inhibition of breast cancer proliferation by combined treatment with 4EGI-1 and MK2206.Cell cycle (Georgetown, Tex.) · 2015Article
- Synthesis of rigidified eIF4E/eIF4G inhibitor-1 (4EGI-1) mimetic and their in vitro characterization as inhibitors of protein-protein interaction.Journal of medicinal chemistry · 2014Article
- Structure-activity relationship study of 4EGI-1, small molecule eIF4E/eIF4G protein-protein interaction inhibitors.European journal of medicinal chemistry · 2014Article
- Proteasome modulates positive and negative translational regulators in long-term synaptic plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Translation of viral mRNAs that do not require eIF4E is blocked by the inhibitor 4EGI-1.Virology · 2013Article
- Multiple components of eIF4F are required for protein synthesis-dependent hippocampal long-term potentiation.Journal of neurophysiology · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The eukaryotic initiation factor eIF4F recruits ribosomes to capped mRNAs while eIF2 mediates start codon recognition to initiate protein synthesis. Increasing interest in targeting translation to suppress tumor growth has led to the development of new classes of inhibitors, including 4EGi-1, which disrupts eIF4F complexes. However, the full effects of this inhibitor and its potential uses in the treatment of other disease states remain unclear. Here, we show that overall rates of protein synthesis in primary human cells were affected only modestly by eIF4F disruption using the mTOR inhibitor Torin1, yet were highly sensitive to 4EGi-1. Translational suppression occurred even at concentrations of 4EGi-1 that were below those required to significantly alter eIF4F levels but were instead found to increase the association of ribosomal complexes containing inactive eIF2α. Although highly stable in culture, the effects of 4EGi-1 on both cellular protein synthesis and ribosome association were readily reversible upon inhibitor removal. In addition, despite potently inhibiting translation, prolonged exposure to 4EGi-1 had only modest effects on cell morphology and protein abundance without affecting viability or stress tolerance to any significant degree, although differential effects on heat shock protein (hsp) expression highlighted distinct 4EGi-1-sensitive modes of hsp induction. In contrast, 4EGi-1 potently suppressed poxvirus replication as well as both reactivation and lytic phases of herpesvirus infection. These findings identify a novel way in which 4EGi-1 affects the host cell's protein synthesis machinery and demonstrate its potential as a noncytotoxic inhibitor of diverse forms of viral infection.
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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.