ArticleMolecular and cellular biology2003
mTOR-dependent regulation of ribosomal gene transcription requires S6K1 and is mediated by phosphorylation of the carboxy-terminal activation domain of the nucleolar transcription factor UBF.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 236 papers.
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The trial behind it
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.
Cardiac Allograft Remodeling and Effects of Sirolimus on Its Progression
A Multicentric, Randomized, Non Comparative, Open-label Phase I/II Evaluating AZD2014 (Dual Mammalian Target of Rapamycin Complex 1/2 (mTORC1/mTORC2) Inhibitor) in Combination With Anastrozole Versus Anastrozole Alone in the Treatment of Metastatic Hormone Receptor-positive Endometrial Adenocarcinoma
Who cites it
236 citing papers in PubMed.
- Regulation of Amino Acid Transporters and Sensors in Response to a High protein Diet: A Randomized Controlled Trial in Elderly Men.The journal of nutrition, health & aging · 2019Trial
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- Ribosome biogenesis is increased in hepatocellular carcinoma and represents a potential therapeutic target.NAR cancer · 2026Article
- Signaling to make human ribosomes: Connections between the cytoplasm and the nucleolus.Molecular cell · 2026Review
- Phosphatidylinositol 4-Kinase IIIβ: A Therapeutic Target for Contractile Dysfunction in Hypertrophic Cardiomyocytes.International journal of molecular sciences · 2026Article
- Combined MYC Activation and PTEN Loss Drives Molecular Features of Aggressive Preinvasive Lesions in Mouse Prostate.Molecular cancer research : MCR · 2026Article
- A metabolism-chromatin axis promotes differential ribosomal RNA transcription in the human malaria parasite.Nature communications · 2025Article
- CDK9 is a dependency in GATA-3 driven and MCL-1 independent T-cell Lymphomas.Blood cancer journal · 2025Article
- Translational Control in Cardiac Pathophysiology and Therapeutic Development: When mRNA Meets the Heart.International journal of molecular sciences · 2025Review
- mTOR pathway diseases: challenges and opportunities from bench to bedside and the mTOR node.Orphanet journal of rare diseases · 2025Review
- The Nucleolus: A Central Hub for Ribosome Biogenesis and Cellular Regulatory Signals.International journal of molecular sciences · 2025Review
- The Central FacilitaTOR: Coordinating Transcription and Translation in Eukaryotes.International journal of molecular sciences · 2025Review
- It Takes a Village of Chromatin Remodelers to Regulate rDNA Expression.International journal of molecular sciences · 2025Review
- mTORC1, the maestro of cell metabolism and growth.Genes & development · 2025Review
- Quantitative label-free digital holographic imaging of cardiomyocyte optical volume, nucleation, and cell division.Journal of molecular and cellular cardiology · 2024Article
- Uncoupling of mTORC1 from E2F activity maintains DNA damage and senescence.Nature communications · 2024Article
- Insulin restores retinal ganglion cell functional connectivity and promotes visual recovery in glaucoma.Science advances · 2024Article
- Targeting mTOR signaling pathways in multiple myeloma: biology and implication for therapy.Cell communication and signaling : CCS · 2024Review
- Article
- Nuclear mTOR Signaling Orchestrates Transcriptional Programs Underlying Cellular Growth and Metabolism.Cells · 2024Review
176 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mammalian target of rapamycin (mTOR) is a key regulator of cell growth acting via two independent targets, ribosomal protein S6 kinase 1 (S6K1) and 4EBP1. While each is known to regulate translational efficiency, the mechanism by which they control cell growth remains unclear. In addition to increased initiation of translation, the accelerated synthesis and accumulation of ribosomes are fundamental for efficient cell growth and proliferation. Using the mTOR inhibitor rapamycin, we show that mTOR is required for the rapid and sustained serum-induced activation of 45S ribosomal gene transcription (rDNA transcription), a major rate-limiting step in ribosome biogenesis and cellular growth. Expression of a constitutively active, rapamycin-insensitive mutant of S6K1 stimulated rDNA transcription in the absence of serum and rescued rapamycin repression of rDNA transcription. Moreover, overexpression of a dominant-negative S6K1 mutant repressed transcription in exponentially growing NIH 3T3 cells. Rapamycin treatment led to a rapid dephosphorylation of the carboxy-terminal activation domain of the rDNA transcription factor, UBF, which significantly reduced its ability to associate with the basal rDNA transcription factor SL-1. Rapamycin-mediated repression of rDNA transcription was rescued by purified recombinant phosphorylated UBF and endogenous UBF from exponentially growing NIH 3T3 cells but not by hypophosphorylated UBF from cells treated with rapamycin or dephosphorylated recombinant UBF. Thus, mTOR plays a critical role in the regulation of ribosome biogenesis via a mechanism that requires S6K1 activation and phosphorylation of UBF.
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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.