ArticleCellular signalling2016
Negative regulation of the FOXO3a transcription factor by mTORC2 induces a pro-survival response following exposure to ultraviolet-B irradiation.
Article in Cellular signalling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Everolimus suppresses glucose transporter 3 membrane trafficking to improve therapeutic efficacy of umbilical cord blood-derived mesenchymal stem cell transplantation in diabetic retinopathy.Cell death & disease · 2026Article
- miR-29a-3p and TGF-β Axis in Fanconi anemia: mechanisms driving metabolic dysfunction and genome stability.Cellular and molecular life sciences : CMLS · 2025Article
- Mitochondrial unfolded protein response in regulatory T cell function: a protective mechanism in immune aging.Frontiers in immunology · 2025Review
- m6A methyltransferase WTAP regulates myocardial ischemia reperfusion injury through YTHDF1/FOXO3a signaling.Apoptosis : an international journal on programmed cell death · 2023Article
- mTORC2 Is the Major Second Layer Kinase Negatively Regulating FOXO3 Activity.Molecules (Basel, Switzerland) · 2022Article
- Review
- mTORC1 and mTORC2 Differentially Regulate Cell Fate Programs to Coordinate Osteoblastic Differentiation in Mesenchymal Stromal Cells.Scientific reports · 2019Article
- Inhibition of mTORC2 enhances UVB-induced apoptosis in keratinocytes through a mechanism dependent on the FOXO3a transcriptional target NOXA but independent of TRAIL.Cellular signalling · 2018Article
- Knockout of Raptor destabilizes ornithine decarboxylase mRNA and decreases binding of HuR to the ODC transcript in cells exposed to ultraviolet-B irradiation.Biochemical and biophysical research communications · 2018Article
- mTOR/AMPK signaling in the brain: Cell metabolism, proteostasis and survival.Current opinion in toxicology · 2018Article
- Mechanistic target of rapamycin complex 1 and 2 in human temporal lobe epilepsy.Annals of neurology · 2018Article
- Caught in the act - protein adaptation and the expanding roles of the PACS proteins in tissue homeostasis and disease.Journal of cell science · 2017Review
- Molecular signaling cascades involved in nonmelanoma skin carcinogenesis.The Biochemical journal · 2016Review
- Erythropoietin and mTOR: A "One-Two Punch" for Aging-Related Disorders Accompanied by Enhanced Life Expectancy.Current neurovascular research · 2016Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Exposure to ultraviolet-B (UVB) irradiation, the principal cause of non-melanoma skin cancer (NMSC), activates both the rapamycin-sensitive mammalian target of rapamycin complex 1 (mTORC1) and the rapamycin-resistant mTORC2. We have previously reported that UVB-induced keratinocyte survival is dependent on mTORC2, though the specific mechanism is not well understood. FOXO3a is an important transcription factor involved in regulating cell survival. The activity of FOXO3a is reduced as a result of protein kinase B (AKT/PKB) activation, which is downstream of mTORC2; however, the specific function of FOXO3a during UVB-induced apoptosis is unclear. In this study, we establish that in cells with wild-type mTORC2 activity, FOXO3a is quickly phosphorylated in response to UVB and sequestered in the cytoplasm. In contrast, loss of mTORC2 causes FOXO3a to be localized to the nucleus and sensitizes cells to UVB-induced apoptosis. Furthermore, this sensitization is rescued by knockdown of FOXO3a. Taken together, these studies provide strong evidence that inhibition of mTORC2 enhances UVB-induced apoptosis in a FOXO3a-dependent manner, and suggest that FOXO3a activation by mTORC2 inhibitors may be a valuable chemopreventive target in NMSC.
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