ArticleProceedings of the National Academy of Sciences of the United States of America2012
DNA damage and eIF4G1 in breast cancer cells reprogram translation for survival and DNA repair mRNAs.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 113 citations in OpenAlex.
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- The Cap-Independent Translation of Survivin 5'UTR and HIV-1 IRES Sequences Is Inhibited by Oxidative Stress Produced byBiomolecules · 2026Article
- Eukaryotic translation initiation factor 4F: functional properties and physiological role.Nucleic acids research · 2025Review
- E0703 targets ERβ to facilitate the upregulation of GLI3, thereby alleviating irradiation-induced DNA damage on lymphocytes.Cellular & molecular biology letters · 2025Article
- The CDK8 kinase module: A novel player in the transcription of translation initiation and ribosomal genes.Molecular biology of the cell · 2025Article
- Comprehensive genomic characterization of early-stage bladder cancer.Nature genetics · 2025Article
- Aurintricarboxylic acid inhibits the malignant phenotypes of drug-resistant cells via translation regulation.Frontiers in oncology · 2025Article
- Proteomic Analysis Reveals Major Proteins and Pathways That Mediate the Effect of 17-β-Estradiol in Cell Division and Apoptosis in Breast Cancer MCF7 Cells.Journal of proteome research · 2024Article
- Non-canonical mRNA translation initiation in cell stress and cancer.NAR cancer · 2024Review
- N-MYC regulates cell survival via eIF4G1 in inv(16) acute myeloid leukemia.Science advances · 2024Article
- Protein Translation in the Pathogenesis of Parkinson's Disease.International journal of molecular sciences · 2024Review
- A Novel HOXA10-Associated 5-Gene-Based Prognostic Signature for Stratification of Short-term Survivors of Pancreatic Ductal Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Paralogous translation factors target distinct mRNAs to differentially regulate tolerance to oxidative stress in yeast.Nucleic acids research · 2023Article
- Breast cancer cell mesenchymal transition and metastasis directed by DAP5/eIF3d-mediated selective mRNA translation.Cell reports · 2023Article
- Specific mechanisms of translation initiation in higher eukaryotes: the eIF4G2 story.RNA (New York, N.Y.) · 2023Review
- EIF4G1 Is a Potential Prognostic Biomarker of Breast Cancer.Biomolecules · 2022Article
- Inhibition of the Translation Initiation Factor eIF4A Enhances Tumor Cell Radiosensitivity.Molecular cancer therapeutics · 2022Article
- TDP1-independent pathways in the process and repair of TOP1-induced DNA damage.Nature communications · 2022Article
- Protein synthesis control in cancer: selectivity and therapeutic targeting.The EMBO journal · 2022Review
- AU-Rich Element RNA Binding Proteins: At the Crossroads of Post-Transcriptional Regulation and Genome Integrity.International journal of molecular sciences · 2021Review
13 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
Abstract
The cellular response to DNA damage is mediated through multiple pathways that regulate and coordinate DNA repair, cell cycle arrest, and cell death. We show that the DNA damage response (DDR) induced by ionizing radiation (IR) is coordinated in breast cancer cells by selective mRNA translation mediated by high levels of translation initiation factor eIF4G1 (eukaryotic initiation factor 4γ1). Increased expression of eIF4G1, common in breast cancers, was found to selectively increase translation of mRNAs involved in cell survival and the DDR, preventing autophagy and apoptosis [Survivin, hypoxia inducible factor 1α (HIF1α), X-linked inhibitor of apoptosis (XIAP)], promoting cell cycle arrest [growth arrest and DNA damage protein 45a (GADD45a), protein 53 (p53), ATR-interacting protein (ATRIP), Check point kinase 1 (Chk1)] and DNA repair [p53 binding protein 1 (53BP1), breast cancer associated proteins 1, 2 (BRCA1/2), Poly-ADP ribose polymerase (PARP), replication factor c2-5 (Rfc2-5), ataxia telangiectasia mutated gene 1 (ATM), meiotic recombination protein 11 (MRE-11), and others]. Reduced expression of eIF4G1, but not its homolog eIF4G2, greatly sensitizes cells to DNA damage by IR, induces cell death by both apoptosis and autophagy, and significantly delays resolution of DNA damage foci with little reduction of overall protein synthesis. Although some mRNAs selectively translated by higher levels of eIF4G1 were found to use internal ribosome entry site (IRES)-mediated alternate translation, most do not. The latter group shows significantly reduced dependence on eIF4E for translation, facilitated by an enhanced requirement for eIF4G1. Increased expression of eIF4G1 therefore promotes specialized translation of survival, growth arrest, and DDR mRNAs that are important in cell survival and DNA repair following genotoxic DNA damage.
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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.