ArticleCell reports2021
Proteomics reveal cap-dependent translation inhibitors remodel the translation machinery and translatome.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 30 citations in OpenAlex.
- Polysomal Profiling Coupled to Allele-Specific Proteomics Reveals an EIF4H TranSNP Allele Possessing Higher mRNA Translation Potential.Molecular & cellular proteomics : MCP · 2026Article
- Nicotinamide N-methyltransferase promotes drug resistance in lung cancer, as revealed by nascent proteomic profiling.Molecular oncology · 2026Article
- Broad-spectrum antiviral activity of the synthetic rocaglate zotatifin against Mayaro virus and other viruses.Frontiers in cellular and infection microbiology · 2026Article
- Peptide antibody tools to dissect specific functions of eIF4A paralogs in cancer.Discover oncology · 2025Article
- Blocking NRF2 Translation by Inhibition of Cap-Dependent Initiation Sensitizes Lymphoma Cells to Ferroptosis and CAR T-cell Immunotherapy.Cancer research · 2025Article
- Discovery of RNA-Protein Molecular Clamps Using Proteome-Wide Stability Assays.Journal of proteome research · 2025Article
- The advances of DEAD-box RNA helicase 17 in chronic non-infectious diseases.Frontiers in cardiovascular medicine · 2025Review
- Discovery of RNA-Protein Molecular Clamps Using Proteome-Wide Stability Assays.bioRxiv : the preprint server for biology · 2024Article
- Targeting cancer stem cells by TPA leads to inhibition of refractory sarcoma and extended overall survival.Molecular therapy. Oncology · 2024Article
- DMDA-PatA mediates RNA sequence-selective translation repression by anchoring eIF4A and DDX3 to GNG motifs.Nature communications · 2024Article
- Protein translation: biological processes and therapeutic strategies for human diseases.Signal transduction and targeted therapy · 2024Review
- RNA helicase EIF4A1-mediated translation is essential for the GC response.Life science alliance · 2024Article
- Targeting eIF4A triggers an interferon response to synergize with chemotherapy and suppress triple-negative breast cancer.The Journal of clinical investigation · 2023Article
- Master Transcription Factor Reprogramming Unleashes Selective Translation Promoting Castration Resistance and Immune Evasion in Lethal Prostate Cancer.Cancer discovery · 2023Article
- Customization of the translational complex regulates mRNA-specific translation to control CNS regeneration.Neuron · 2023Article
- Article
- Review
- eIF4A1-dependent mRNAs employ purine-rich 5'UTR sequences to activate localised eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation.Nucleic acids research · 2023Article
- Oncogenic PKA signaling increases c-MYC protein expression through multiple targetable mechanisms.eLife · 2023Article
- The flavagline FL3 interferes with the association of Annexin A2 with the eIF4F initiation complex and transiently stimulates the translation ofFrontiers in cell and developmental biology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Tactical disruption of protein synthesis is an attractive therapeutic strategy, with the first-in-class eIF4A-targeting compound zotatifin in clinical evaluation for cancer and COVID-19. The full cellular impact and mechanisms of these potent molecules are undefined at a proteomic level. Here, we report mass spectrometry analysis of translational reprogramming by rocaglates, cap-dependent initiation disruptors that include zotatifin. We find effects to be far more complex than simple "translational inhibition" as currently defined. Translatome analysis by TMT-pSILAC (tandem mass tag-pulse stable isotope labeling with amino acids in cell culture mass spectrometry) reveals myriad upregulated proteins that drive hitherto unrecognized cytotoxic mechanisms, including GEF-H1-mediated anti-survival RHOA/JNK activation. Surprisingly, these responses are not replicated by eIF4A silencing, indicating a broader translational adaptation than currently understood. Translation machinery analysis by MATRIX (mass spectrometry analysis of active translation factors using ribosome density fractionation and isotopic labeling experiments) identifies rocaglate-specific dependence on specific translation factors including eEF1ε1 that drive translatome remodeling. Our proteome-level interrogation reveals that the complete cellular response to these historical "translation inhibitors" is mediated by comprehensive translational landscape remodeling.
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.