ArticleCell chemical biology2021
Dual targeting of DDX3 and eIF4A by the translation inhibitor rocaglamide A.
Article in Cell chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 88 citations in OpenAlex.
- The cellular landscape of druggable RNA-binding proteins.Nature reviews. Drug discovery · 2026Review
- Halting translation by the letter with sequence-selective small molecules.Nature chemical biology · 2026Review
- A Dimeric Protein-RNA Glue Promotes Multivalent eIF4A-RNA Assembly.ACS central science · 2026Article
- Paediatric therapeutic development workshop on osteosarcoma.British journal of cancer · 2026Review
- Molecular insights into DDX3X-androgen receptor mRNA regulation via non-canonical G-quadruplex in castration-resistant prostate cancer.Oncogene · 2026Article
- Identification and optimization of first-in-class RNA helicase inhibitors of DDX1, LGP2, and MDA5.European journal of medicinal chemistry · 2026Article
- A Dimeric Rocaglate Promotes Multivalent eIF4A-RNA Assembly.bioRxiv : the preprint server for biology · 2026Article
- Broad-spectrum antiviral activity of the synthetic rocaglate zotatifin against Mayaro virus and other viruses.Frontiers in cellular and infection microbiology · 2026Article
- Genomic and translational insights into eIF2B-mediated salt tolerance in sea rice HD961.BMC biology · 2025Article
- Blocking NRF2 Translation by Inhibition of Cap-Dependent Initiation Sensitizes Lymphoma Cells to Ferroptosis and CAR T-cell Immunotherapy.Cancer research · 2025Article
- Translation Inhibition by Rocaglamide A Enhances Susceptibility of Yeasts to Caspofungin.bioRxiv : the preprint server for biology · 2025Article
- Connecting chemical structure to single cell signaling profiles.Communications biology · 2025Article
- Rapid depletion and super-resolution microscopy reveal dual roles of SRSF5 in coordinating nuclear speckle-paraspeckle crosstalk during cellular stress.Nucleic acids research · 2025Article
- Targeting eIF4A with RNA Aptamers Enhances Salt Stress Tolerance in Rice Through Modulation of Translation Initiation.Rice (New York, N.Y.) · 2025Article
- Aptamer‑mediated modulation of eEF1 enhances salt stress tolerance in rice.BMC plant biology · 2025Article
- Targeting translation initiation yields fast-killing therapeutics against the zoonotic parasite Cryptosporidium parvum.PLoS pathogens · 2025Article
- Advances in ribosome profiling technologies.Biochemical Society transactions · 2025Review
- Role of DEAD/DEAH-box helicases in immunity, infection and cancers.Cell communication and signaling : CCS · 2025Review
- Discovery of RNA-Protein Molecular Clamps Using Proteome-Wide Stability Assays.Journal of proteome research · 2025Article
- The DEAD-box helicase eIF4A1/2 acts as RNA chaperone during mitotic exit enabling chromatin decondensation.Nature communications · 2025Article
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
The translation inhibitor rocaglamide A (RocA) has shown promising antitumor activity because it uniquely clamps eukaryotic initiation factor (eIF) 4A onto polypurine RNA for selective translational repression. As eIF4A has been speculated to be a unique target of RocA, alternative targets have not been investigated. Here, we reveal that DDX3 is another molecular target of RocA. Proximity-specific fluorescence labeling of an O-nitrobenzoxadiazole-conjugated derivative revealed that RocA binds to DDX3. RocA clamps the DDX3 protein onto polypurine RNA in an ATP-independent manner. Analysis of a de novo-assembled transcriptome from the plant Aglaia, a natural source of RocA, uncovered the amino acid critical for RocA binding. Moreover, ribosome profiling showed that because of the dominant-negative effect of RocA, high expression of eIF4A and DDX3 strengthens translational repression in cancer cells. This study indicates that sequence-selective clamping of DDX3 and eIF4A, and subsequent dominant-negative translational repression by RocA determine its tumor toxicity.
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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.