ArticleThe Journal of biological chemistry2016
Nrf2 Transcription Factor Can Directly Regulate mTOR: LINKING CYTOPROTECTIVE GENE EXPRESSION TO A MAJOR METABOLIC REGULATOR THAT GENERATES REDOX ACTIVITY.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 94 citations in OpenAlex.
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- Oxidative Stress-Driven Cellular Senescence: Mechanistic Crosstalk and Therapeutic Horizons.Antioxidants (Basel, Switzerland) · 2025Review
- An Update on Role of Ionizing Radiation to Enhance Proliferation and Differentiation of Normal Stem Cells via Activation of NRF2 Pathway: Review.Antioxidants (Basel, Switzerland) · 2025Review
- Folic Acid Alleviates Hydrogen Peroxide-Induced Oxidative Stress in Bovine Placental Trophoblast Cells by Regulating the NRF2/mTOR Signaling Pathway.International journal of molecular sciences · 2025Article
- Pexophagy and Oxidative Stress: Focus on Peroxisomal Proteins and Reactive Oxygen Species (ROS) Signaling Pathways.Antioxidants (Basel, Switzerland) · 2025Review
- The molecular determinants regulating redox signaling in diabetic endothelial cells.Frontiers in pharmacology · 2025Review
- Molecular mechanism on autophagy associated cardiovascular dysfunction inFrontiers in cell and developmental biology · 2025Review
- Imbalance of redox homeostasis and altered cellular signaling induced by the metal complexes of terpyridine.Scientific reports · 2024Article
- Tetramethylpyrazine Analogue T-006 Protects Neuronal and Endothelial Cells Against Oxidative Stress via PI3K/AKT/mTOR and Nrf2 Signaling.Antioxidants (Basel, Switzerland) · 2024Article
- Glucose deprivation triggers DCAF1-mediated inactivation of Rheb-mTORC1 and promotes cancer cell survival.Cell death & disease · 2024Article
- Beta-Hydroxybutyrate Mitigates Sensorimotor and Cognitive Impairments in a Photothrombosis-Induced Ischemic Stroke in Mice.International journal of molecular sciences · 2024Article
- Characterization of a Clinically and Biologically Defined Subgroup of Patients with Autism Spectrum Disorder and Identification of a Tailored Combination Treatment.Biomedicines · 2024Article
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- Neuroprotection during Thrombectomy for Acute Ischemic Stroke: A Review of Future Therapies.International journal of molecular sciences · 2024Review
- Regulatory factors of Nrf2 in age-related macular degeneration pathogenesis.International journal of ophthalmology · 2024Review
- Hyperbaric oxygen treatment increases intestinal stem cell proliferation through the mTORC1/S6K1 signaling pathway in Mus musculus.Biological research · 2023Article
- Discovery of New 2-Phenylamino-3-acyl-1,4-naphthoquinones as Inhibitors of Cancer Cells Proliferation: Searching for Intra-Cellular Targets Playing a Role in Cancer Cells Survival.Molecules (Basel, Switzerland) · 2023Article
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5 authors at 1 institution in 1 country.
Funding
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Abstract
Nrf2 is a master transcription factor that regulates a wide variety of cellular proteins by recognizing and binding to antioxidant response elements (AREs) in their gene promoter regions. In this study we show that increasing cellular Nrf2 results in transcriptional activation of the gene for mTOR, which is central to the PI3K signaling pathway. This is the case in cells with normal physiological PI3K. However, in cells with abnormally active PI3K increased cellular Nrf2 levels have no effect on mTOR. ChIP assays results show that increased Nrf2 binding is associated with decreased p65 binding and H3-K27me3 signal (marker of gene repression) as well as increased H3-K4me3 signal (marker of gene activation). However, in cells with PI3K activation, no effect of cellular Nrf2 increase on mTOR transcription was observed. In these cells, increasing Nrf2 levels increases Nrf2 promoter binding marginally, whereas p65 binding and H3-K27me3 mark were significantly increased, and H3-K4me3 signal is reduced. Together, these data show for the first time that Nrf2 directly regulates mTOR transcription when the PI3K pathway is intact, whereas this function is lost when PI3K is activated. We have identified a link between the Nrf2 system of sensing environmental stress and mTOR, which is a key cellular protein in metabolism. Studies in cells with activating mutations in the PI3K pathway suggest that Nrf2 transcriptional regulation of mTOR is related to promoter binding of p65 and of methylation of histone residues permissive of transcription.
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