ArticleOncotarget2017
P53 suppresses ribonucleotide reductase via inhibiting mTORC1.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- Ribonucleotide Reductase Inhibition Triggers Ferroptosis in Genetically Defined Subsets of Non-Small Cell Lung Cancer.Cancer research communications · 2026Article
- TP53 Loss Fuels mTORC1 Activation and Autophagy Suppression to Drive Immune-Cold Colorectal Cancer.World journal of oncology · 2026Article
- Ribonucleotide reductase subunit M2 mediates the mTOR pathway to recruit furin endoprotease and promote maturation of dengue virus.iScience · 2025Article
- R-loop formation contributes to mTORC1 activation-dependent DNA replication stress induced by p53 deficiency.Acta biochimica et biophysica Sinica · 2024Article
- Understanding the interplay between dNTP metabolism and genome stability in cancer.Disease models & mechanisms · 2024Review
- Altered CELF4 splicing factor enhances pancreatic neuroendocrine tumors aggressiveness influencing mTOR and everolimus response.Molecular therapy. Nucleic acids · 2024Article
- Ribonucleotide reductase M2 (RRM2): Regulation, function and targeting strategy in human cancer.Genes & diseases · 2024Review
- Regulatory Role of Ribonucleotide Reductase Subunit M2 in Hepatocyte Growth and Pathogenesis of Hepatitis C Virus.International journal of molecular sciences · 2023Review
- The complexity of p53-mediated metabolic regulation in tumor suppression.Seminars in cancer biology · 2022Review
- P53 maintains gallid alpha herpesvirus 1 replication by direct regulation of nucleotide metabolism and ATP synthesis through its target genes.Frontiers in microbiology · 2022Article
- Narrative review of emerging roles for AKT-mTOR signaling in cancer radioimmunotherapy.Annals of translational medicine · 2021Review
- Increased p53 signaling impairs neural differentiation in HUWE1-promoted intellectual disabilities.Cell reports. Medicine · 2021Article
- Regulation of DNA duplication by the mTOR signaling pathway.Cell cycle (Georgetown, Tex.) · 2021Review
- The translational repressor 4E-BP1 regulates RRM2 levels and functions as a tumor suppressor in Ewing sarcoma tumors.Oncogene · 2021Article
- Comprehensive Analysis of Cyclin Family Gene Expression in Colon Cancer.Frontiers in oncology · 2021Article
- Cyclin F is involved in response to cisplatin treatment in melanoma cell lines.Oncology reports · 2020Article
- Metabolic functions of the tumor suppressor p53: Implications in normal physiology, metabolic disorders, and cancer.Molecular metabolism · 2020Review
- mTOR inhibition overcomes primary and acquired resistance to Wee1 inhibition by augmenting replication stress in epithelial ovarian cancers.American journal of cancer research · 2020Article
- Potential mechanism of RRM2 for promoting Cervical Cancer based on weighted gene co-expression network analysis.International journal of medical sciences · 2020Article
- mTOR Signaling Upregulates CDC6 via Suppressing miR-3178 and Promotes the Loading of DNA Replication Helicase.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Balanced deoxyribonucleotides pools are essential for cell survival and genome stability. Ribonucleotide reductase is the rate-limiting enzyme for the production of deoxyribonucleotides. We report here that p53 suppresses ribonucleotide reductase subunit 1 (RRM1) and 2 (RRM2) via inhibiting mammalian target of rapamycin complex 1 (mTORC1). In vitro, cancer cell lines and mouse embryonic fibroblast cells were treated with different concentrations of pharmacological inhibitors for different times. In vivo, rhabdomyosarcoma Rh30 cell tumor-bearing mice were treated with rapamycin or AZD8055. Protein levels and phosphorylation status were assessed by immunoblotting and mRNA levels were determined by real time RT-PCR. Pharmacological inhibition of mTORC1 with rapamycin, mTOR kinase with AZD8055 or protein kinase B with MK2206 resulted in decrease of RRM1 and RRM2 in Rh30 cells both in vitro and in mouse tumor xenografts. Moreover, eukaryotic translational initiation factor 4E-binding proteins 1 and 2 double knockout mouse embryonic fibroblast cells demonstrated an elevation of RRM1 and RRM2. Furthermore, down-regulation of mTOR-protein kinase B signaling or cyclin dependent kinase 4 led to decrease of RRM1 and RRM2 mRNAs. In addition, TP53 mutant cancer cells had elevation of RRM1 and RRM2, which was reduced by rapamycin. Importantly, human double minute 2 inhibitor nutlin-3 decreased RRM1 and RRM2 in TP53 wild type rhabdomyosarcoma Rh18 but not in TP53 mutated Rh30 cells. Our data demonstrated that mTOR enhances the cap-dependent protein translation and gene transcription of RRM1 and RRM2. Our findings might provide an additional mechanism by which p53 maintains genome stability.
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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.