ArticleThe Journal of biological chemistry2012
Role of p70S6K1-mediated phosphorylation of eIF4B and PDCD4 proteins in the regulation of protein synthesis.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
- Gene expression regulation by CaCellular & molecular biology letters · 2026Pooled it
- Autophagy-Lysosomal Axis Stimulation by Beta-Hydroxybutyrate in Astrocytes.Molecular neurobiology · 2026Article
- Molecular alterations in MAPK/ERK, β-Catenin/Wnt, and PI3K/mTOR pathways in adenomatoid odontogenic tumor.Journal of applied oral science : revista FOB · 2026Article
- Eukaryotic translation initiation factor 4F: functional properties and physiological role.Nucleic acids research · 2025Review
- Cell Type-Specific mTORC1 Signaling and Translational Control in Synaptic Plasticity and Memory.Journal of neurochemistry · 2025Review
- Signaling networks governing skeletal muscle growth, atrophy, and cachexiaSkeletal muscle · 2025Review
- ER-phagy Activation by AMFR Attenuates Cardiac Fibrosis Post-Myocardial Infarction via mTORC1 Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- TBCK Deficiency Alters Ribosomal Function, RNA Splicing, and miRNA Networks: Insights from Multi-Omics Analyses.bioRxiv : the preprint server for biology · 2025Article
- Translational control of innate barrier defense by the gut microbiota.bioRxiv : the preprint server for biology · 2025Article
- Footprints in the Sno: investigating the cellular and molecular mechanisms of SNORD116.Open biology · 2025Review
- Monocyte eukaryotic initiation factor 2 signaling differentiates 17-hydroxy-docosahexaenoic acid levels and pain.iScience · 2025Article
- Quantitative Proteomic Study Reveals Amygdalin Alleviates Liver Fibrosis Through Inhibiting mTOR/PDCD4/JNK Pathway in Hepatic Stellate Cells.Drug design, development and therapy · 2025Article
- Targeting mTOR signaling pathways in multiple myeloma: biology and implication for therapy.Cell communication and signaling : CCS · 2024Review
- YANK2 activated by Fyn promotes glioma tumorigenesis via the mTOR-independent p70S6K activation pathway.Scientific reports · 2024Article
- 2-methoxyestradiol inhibits the malignant behavior of triple negative breast cancer cells by altering their miRNome.Frontiers in oncology · 2024Article
- TDP-43 protein interactome informs about perturbed canonical pathways and may help develop personalized medicine approaches for patients with TDP-43 pathology.Drug discovery today · 2023Review
- Long Non-Coding RNAs (lncRNAs) as Regulators of the PI3K/AKT/mTOR Pathway in Gastric Carcinoma.International journal of molecular sciences · 2023Review
- Loss of 4E-BPs prevents the hindlimb immobilization-induced decrease in protein synthesis in skeletal muscle.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Article
- Protein translation paradox: Implications in translational regulation of aging.Frontiers in cell and developmental biology · 2023Review
- Leucine Supplementation in Cancer Cachexia: Mechanisms and a Review of the Pre-Clinical Literature.Nutrients · 2022Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Modulation of mRNA binding to the 40 S ribosomal subunit during translation initiation controls not only global rates of protein synthesis but also regulates the pattern of protein expression by allowing for selective inclusion, or exclusion, of mRNAs encoding particular proteins from polysomes. The mRNA binding step is modulated by signaling through a protein kinase known as the mechanistic target of rapamycin complex 1 (mTORC1). mTORC1 directly phosphorylates the translational repressors eIF4E binding proteins (4E-BP) 1 and 2, releasing them from the mRNA cap binding protein eIF4E, thereby promoting assembly of the eIF4E·eIF4G complex. mTORC1 also phosphorylates the 70-kDa ribosomal protein S6 kinase 1 (p70S6K1), which subsequently phosphorylates eIF4B, and programmed cell death 4 (PDCD4), which sequesters eIF4A from the eIF4E·eIF4G complex, resulting in repressed translation of mRNAs with highly structured 5'-untranslated regions. In the present study, we compared the role of the 4E-BPs in the regulation of global rates of protein synthesis to that of eIF4B and PDCD4. We found that maintenance of eIF4E interaction with eIF4G was not by itself sufficient to sustain global rates of protein synthesis in the absence of mTORC1 signaling to p70S6K1; phosphorylation of both eIF4B and PDCD4 was additionally required. We also found that the interaction of eIF4E with eIF4G was maintained in the liver of fasted rats as well as in serum-deprived mouse embryo fibroblasts lacking both 4E-BP1 and 4E-BP2, suggesting that the interaction of eIF4G with eIF4E is controlled primarily through the 4E-BPs.
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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.