ArticleJournal of molecular cell biology2014
Oxygen sufficiency controls TOP mRNA translation via the TSC-Rheb-mTOR pathway in a 4E-BP-independent manner.
Article in Journal of molecular cell biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 85 citations in OpenAlex.
- Metabolic and transcriptional plasticity supports CD8Immunity · 2026Article
- Identification of biomarkers and potential drug targets in DFU based on fundamental experiments and multi-omics joint analysis.Frontiers in pharmacology · 2025Article
- Distinct roles of LARP1 and 4EBP1/2 in regulating translation and stability of 5'TOP mRNAs.Science advances · 2024Article
- Novel 4th-generation phytase improves broiler growth performance and reduces woody breast severity through modulation of muscle glucose uptake and metabolism.Frontiers in physiology · 2024Article
- LARP1 senses free ribosomes to coordinate supply and demand of ribosomal proteins.bioRxiv : the preprint server for biology · 2023Article
- Characteristics and anatomic location of PD-1Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The coordinated management of ribosome and translation during injury and regeneration.Frontiers in cell and developmental biology · 2023Review
- Targeting mTOR as a Cancer Therapy: Recent Advances in Natural Bioactive Compounds and Immunotherapy.Cancers · 2022Review
- T-Cell Intracellular Antigen 1-Like Protein in Physiology and Pathology.International journal of molecular sciences · 2022Review
- Protein synthesis control in cancer: selectivity and therapeutic targeting.The EMBO journal · 2022Review
- The Multifunctional Faces of T-Cell Intracellular Antigen 1 in Health and Disease.International journal of molecular sciences · 2022Review
- Blocking the Farnesyl Pocket of PDEδ Reduces Rheb-Dependent mTORC1 Activation and Survival ofFrontiers in pharmacology · 2022Article
- Upregulation of RNA cap methyltransferase RNMT drives ribosome biogenesis during T cell activation.Nucleic acids research · 2021Article
- mTORC1 promotes TOP mRNA translation through site-specific phosphorylation of LARP1.Nucleic acids research · 2021Article
- Controversies around the function of LARP1.RNA biology · 2021Review
- Upregulation of 5'-terminal oligopyrimidine mRNA translation upon loss of the ARF tumor suppressor.Scientific reports · 2020Article
- TOP mRNPs: Molecular Mechanisms and Principles of Regulation.Biomolecules · 2020Review
- A post-transcriptional program of chemoresistance by AU-rich elements and TTP in quiescent leukemic cells.Genome biology · 2020Article
- Mitosis-related phosphorylation of the eukaryotic translation suppressor 4E-BP1 and its interaction with eukaryotic translation initiation factor 4E (eIF4E).The Journal of biological chemistry · 2019Article
- Distinct Cancer-Promoting Stromal Gene Expression Depending on Lung Function.American journal of respiratory and critical care medicine · 2019Article
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Authors and funding
15 authors at 7 institutions in 5 countries.
Funding
Abstract
Cells encountering hypoxic stress conserve resources and energy by downregulating the protein synthesis. Here we demonstrate that one mechanism in this response is the translational repression of TOP mRNAs that encode components of the translational apparatus. This mode of regulation involves TSC and Rheb, as knockout of TSC1 or TSC2 or overexpression of Rheb rescued TOP mRNA translation in oxygen-deprived cells. Stress-induced translational repression of these mRNAs closely correlates with the hypophosphorylated state of 4E-BP, a translational repressor. However, a series of 4E-BP loss- and gain-of-function experiments disprove a cause-and-effect relationship between the phosphorylation status of 4E-BP and the translational repression of TOP mRNAs under oxygen or growth factor deprivation. Furthermore, the repressive effect of anoxia is similar to that attained by the very efficient inhibition of mTOR activity by Torin 1, but much more pronounced than raptor or rictor knockout. Likewise, deficiency of raptor or rictor, even though it mildly downregulated basal translation efficiency of TOP mRNAs, failed to suppress the oxygen-mediated translational activation of TOP mRNAs. Finally, co-knockdown of TIA-1 and TIAR, two RNA-binding proteins previously implicated in translational repression of TOP mRNAs in amino acid-starved cells, failed to relieve TOP mRNA translation under other stress conditions. Thus, the nature of the proximal translational regulator of TOP mRNAs remains elusive.
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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.