ArticleProceedings of the National Academy of Sciences of the United States of America2016
Importin 8 mediates m7G cap-sensitive nuclear import of the eukaryotic translation initiation factor eIF4E.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. 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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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
48 citing papers in PubMed, 59 citations in OpenAlex.
- Trial
- Escorting mRNAs - the multifunctional and divergent roles of cap-chaperones in post-transcriptional gene expression.Journal of cell science · 2026Review
- ABHD11-AS1 Suppresses Colorectal Cancer Progression by Disrupting EIF4E-mediated POU2F1 Ubiquitination.International journal of biological sciences · 2026Article
- Multipurpose RNA maturation factors dysregulate multiple mRNA processing steps simultaneously and provide new therapeutic opportunities.RNA biology · 2025Review
- Transcriptomic and proteomic analyses of SH-SY5Y neuroblastoma cells treated with amisulpride.Acta neuropsychiatrica · 2025Article
- RNA epigenetic modifications as dynamic biomarkers in cancer: from mechanisms to clinical translation.Biomarker research · 2025Review
- Targeting colorectal cancer at the level of nuclear pore complex.Journal of advanced research · 2025Review
- The inspiration of methyltransferase in RNA methylation modification for targeted therapy of malignant tumors.Frontiers in immunology · 2025Review
- The role of m5C, m1A and m7G modifications in tumors of urinary system.Frontiers in cell and developmental biology · 2025Review
- eIF4E orchestrates mRNA processing, RNA export and translation to modify specific protein production.Nucleus (Austin, Tex.) · 2024Review
- RNA modifications: emerging players in the regulation of reproduction and development.Acta biochimica et biophysica Sinica · 2024Review
- Nuclear localization signal-tagged systems: relevant nuclear import principles in the context of current therapeutic design.Chemical Society reviews · 2024Review
- M7G-related tumor immunity: novel insights of RNA modification and potential therapeutic targets.International journal of biological sciences · 2024Review
- 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
- Nuclear transport proteins: structure, function, and disease relevance.Signal transduction and targeted therapy · 2023Review
- RNA modifications in cancer.British journal of cancer · 2023Review
- Proteomics of Plasma and Plasma-Treated Podocytes: Application to Focal and Segmental Glomerulosclerosis.International journal of molecular sciences · 2023Article
- The eukaryotic translation initiation factor eIF4E reprograms alternative splicing.The EMBO journal · 2023Article
- Biological functions and research progress of eIF4E.Frontiers in oncology · 2023Review
- Shining a spotlight on m6A and the vital role of RNA modification in endometrial cancer: a review.Frontiers in genetics · 2023Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Regulation of nuclear-cytoplasmic trafficking of oncoproteins is critical for growth homeostasis. Dysregulated trafficking contributes to malignancy, whereas understanding the process can reveal unique therapeutic opportunities. Here, we focus on eukaryotic translation initiation factor 4E (eIF4E), a prooncogenic protein highly elevated in many cancers, including acute myeloid leukemia (AML). Typically, eIF4E is localized to both the nucleus and cytoplasm, where it acts in export and translation of specific methyl 7-guanosine (m(7)G)-capped mRNAs, respectively. Nuclear accumulation of eIF4E in patients who have AML is correlated with increased eIF4E-dependent export of transcripts encoding oncoproteins. The subcellular localization of eIF4E closely correlates with patients' responses. During clinical responses to the m(7)G-cap competitor ribavirin, eIF4E is mainly cytoplasmic. At relapse, eIF4E reaccumulates in the nucleus, leading to elevated eIF4E-dependent mRNA export. We have identified importin 8 as a factor that directly imports eIF4E into the nucleus. We found that importin 8 is highly elevated in untreated patients with AML, leading to eIF4E nuclear accumulation. Importin 8 only imports cap-free eIF4E. Cap-dependent changes to the structure of eIF4E underpin this selectivity. Indeed, m(7)G cap analogs or ribavirin prevents nuclear entry of eIF4E, which mirrors the trafficking phenotypes observed in patients with AML. Our studies also suggest that nuclear entry is important for the prooncogenic activity of eIF4E, at least in this context. These findings position nuclear trafficking of eIF4E as a critical step in its regulation and position the importin 8-eIF4E complex as a novel therapeutic target.
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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.