ArticlePloS one2014
The mTOR pathway controls cell proliferation by regulating the FoxO3a transcription factor via SGK1 kinase.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 100 citations in OpenAlex.
- Defective Neural Stem and Progenitor Cell Proliferation in Neurodevelopmental Disorders.Journal of developmental biology · 2025Review
- A mechanistic computational model of HGF-VEGF-mediated endothelial cell proliferation and vascular permeability.iScience · 2025Article
- FoxO3 Activation Alleviates Doxorubicin-Induced Cardiomyopathy by Enhancing Autophagic Flux and Suppressing mTOR/ROS Signalling.Journal of cellular and molecular medicine · 2025Article
- Phosphorylation of an RNA-Binding Protein Rck/Me31b by Hippo Is Essential for Adipose Tissue Aging.Aging cell · 2025Article
- Modulation of gene expression in immune-related organs by in ovo stimulation with probiotics and prophybiotics in broiler chickens.Journal of applied genetics · 2025Article
- Stage-resolved transcriptomic profiling ofFrontiers in insect science · 2025Article
- Adipose Tissues Have Been Overlooked as Players in Prostate Cancer Progression.International journal of molecular sciences · 2024Review
- SGK1 promotes the lipid accumulation via regulating the transcriptional activity of FOXO1 in bovine.BMC genomics · 2024Article
- Proteobacteria impair anti-tumor immunity in the omentum by consuming arginine.Cell host & microbe · 2024Article
- P53 Activation Promotes Maturational Characteristics of Pluripotent Stem Cell-Derived Cardiomyocytes in 3-Dimensional Suspension Culture Via FOXO-FOXM1 Regulation.Journal of the American Heart Association · 2024Article
- Yohimbine Inhibits PDGF-Induced Vascular Smooth Muscle Cell Proliferation and Migration via FOXO3a Factor.International journal of molecular sciences · 2024Article
- Long-Term Epigenetic Regulation ofInternational journal of molecular sciences · 2024Article
- mTORC1 controls murine postprandial hepatic glycogen synthesis via Ppp1r3b.The Journal of clinical investigation · 2024Article
- mTORC2: a multifaceted regulator of autophagy.Cell communication and signaling : CCS · 2023Review
- Functional role of MicroRNA/PI3K/AKT axis in osteosarcoma.Frontiers in oncology · 2023Review
- Identification ofInternational journal of molecular sciences · 2022Article
- Differential expression of gene co-expression networks related to the mTOR signaling pathway in bipolar disorder.Translational psychiatry · 2022Article
- Human endothelial cell-derived exosomal microRNA-99a/b drives a sustained inflammatory response during sepsis by inhibiting mTOR expression.Frontiers in cellular and infection microbiology · 2022Article
- Arterial cyclic stretch regulates Lamtor1 and promotes neointimal hyperplasia via circSlc8a1/miR-20a-5p axis in vein grafts.Theranostics · 2022Article
- Role of PI3K-AKT-mTOR Pathway as a Pro-Survival Signaling and Resistance-Mediating Mechanism to Therapy of Prostate Cancer.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanistic target of rapamycin (mTOR) functions as a component of two large complexes, mTORC1 and mTORC2, which play crucial roles in regulating cell growth and homeostasis. However, the molecular mechanisms by which mTOR controls cell proliferation remain elusive. Here we show that the FoxO3a transcription factor is coordinately regulated by mTORC1 and mTORC2, and plays a crucial role in controlling cell proliferation. To dissect mTOR signaling, mTORC1 was specifically inactivated by depleting p18, an essential anchor of mTORC1 on lysosomes. mTORC1 inactivation caused a marked retardation of cell proliferation, which was associated with upregulation of cyclin-dependent kinase inhibitors (CDKIs). Although Akt was activated by mTORC1 inactivation, FoxO3a was upregulated via an epigenetic mechanism and hypophosphorylated at Ser314, which resulted in its nuclear accumulation. Consistently, mTORC1 inactivation induced downregulation of serum- and glucocorticoid-inducible kinase 1 (SGK1), the kinase responsible for Ser314 phosphorylation. Expression of FoxO3a mutated at Ser314 suppressed cell proliferation by inducing CDKI expression. SGK1 overexpression suppressed CDKI expression in p18-deficient cells, whereas SGK1 knockdown induced CDKI expression in wild-type cells, resulting in the suppression of cell proliferation. These results suggest that mTORC1, in coordination with mTORC2, controls cell proliferation by regulating FoxO3a gene expression and SGK1-mediated phosphorylation of FoxO3a at Ser314.
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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.