ArticleThe EMBO journal2010
S6K1 is a multifaceted regulator of Mdm2 that connects nutrient status and DNA damage response.
Article in The EMBO journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 127 citations in OpenAlex.
- Downregulation of mTORC1 Signaling is Associated with Increased Sensitivity to Protein Synthesis Perturbations in Multiple Myeloma.ACS omega · 2026Article
- S6K1 Modulates STAT3 Activation to Promote Resistance to Radiotherapy in Lung Cancer.International journal of molecular sciences · 2026Article
- Nucleolus as a cornerstone linking proliferation and metabolism to cellular responses to stress: involvement of transcription factors MYC and p53.Frontiers in molecular biosciences · 2026Review
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Polydatin: A natural compound with multifaceted anticancer properties.Journal of traditional and complementary medicine · 2025Review
- Review
- R-loop formation contributes to mTORC1 activation-dependent DNA replication stress induced by p53 deficiency.Acta biochimica et biophysica Sinica · 2024Article
- S6K1 Controls DNA Damage Signaling Modulated by the MRN Complex to Induce Radioresistance in Lung Cancer.International journal of molecular sciences · 2024Article
- The Dominant Mechanism of Cyclophosphamide-Induced Damage to Ovarian Reserve: Premature Activation or Apoptosis of Primordial Follicles?Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- Interaction between Rumen Epithelial miRNAs-Microbiota-Metabolites in Response to Cold-Season Nutritional Stress in Tibetan Sheep.International journal of molecular sciences · 2023Article
- Radiotherapy and radio-sensitization in H3CNS neuroscience & therapeutics · 2023Review
- Claspin is Required for Growth Recovery from Serum Starvation through Regulating the PI3K-PDK1-mTOR Pathway in Mammalian Cells.Molecular and cellular biology · 2023Article
- Metabolic disorders sensitise endometrial carcinoma through endoplasmic reticulum stress.Cellular & molecular biology letters · 2022Article
- Article
- The complexity of p53-mediated metabolic regulation in tumor suppression.Seminars in cancer biology · 2022Review
- The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products.Antioxidants (Basel, Switzerland) · 2022Review
- Beyond controlling cell size: functional analyses of S6K in tumorigenesis.Cell death & disease · 2022Review
- Age-Related Lysosomal Dysfunctions.Cells · 2022Review
- The Translational Regulation in mTOR Pathway.Biomolecules · 2022Review
- It's Getting Complicated-A Fresh Look at p53-MDM2-ARF Triangle in Tumorigenesis and Cancer Therapy.Frontiers in cell and developmental biology · 2022Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
p53 mediates DNA damage-induced cell-cycle arrest, apoptosis, or senescence, and it is controlled by Mdm2, which mainly ubiquitinates p53 in the nucleus and promotes p53 nuclear export and degradation. By searching for the kinases responsible for Mdm2 S163 phosphorylation under genotoxic stress, we identified S6K1 as a multifaceted regulator of Mdm2. DNA damage activates mTOR-S6K1 through p38alpha MAPK. The activated S6K1 forms a tighter complex with Mdm2, inhibits Mdm2-mediated p53 ubiquitination, and promotes p53 induction, in addition to phosphorylating Mdm2 on S163. Deactivation of mTOR-S6K1 signalling leads to Mdm2 nuclear translocation, which is facilitated by S163 phosphorylation, a reduction in p53 induction, and an alteration in p53-dependent cell death. These findings thus establish mTOR-S6K1 as a novel regulator of p53 in DNA damage response and likely in tumorigenesis. S6K1-Mdm2 interaction presents a route for cells to incorporate the metabolic/energy cues into DNA damage response and links the aging-controlling Mdm2-p53 and mTOR-S6K pathways.
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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.