ArticleMolecular cancer2013
DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-SIN1 association mediates ultraviolet B (UVB)-induced Akt Ser-473 phosphorylation and skin cell survival.
Article in Molecular cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 58 citations in OpenAlex.
- Protein Post-Translational Modifications in UV-Induced Skin Damage.Experimental dermatology · 2026Review
- Impeding the NHEJ Pathway for Overcoming Radioresistance in the Context of Precision Radiotherapy of Cancer.Pharmaceutics · 2026Review
- Hyaluronic acid modified chuanxiong oil liposomes as a novel therapeutic agent for photoaging prevention.Scientific reports · 2025Article
- Synthetic rescue of Xeroderma Pigmentosum C phenotype via PIK3C3 downregulation.Cell death & disease · 2024Article
- PRKDC Induces Chemoresistance in Osteosarcoma by Recruiting GDE2 to Stabilize GNAS and Activate AKT.Cancer research · 2024Article
- Discovery of the DNA-PKcs inhibitor DA-143 which exhibits enhanced solubility relative to NU7441.Scientific reports · 2024Article
- Spatiotemporal roles of AMPK in PARP-1- and autophagy-dependent retinal pigment epithelial cell death caused by UVA.Journal of biomedical science · 2023Article
- Molecular mechanism underlying epithelial-mesenchymal transformation and cisplatin resistance in esophageal squamous cell carcinoma.Thoracic cancer · 2023Review
- Unmasking the tumourigenic role of SIN1/MAPKAP1 in the mTOR complex 2.Clinical and translational medicine · 2023Review
- DNA damage repair kinase DNA-PK and cGAS synergize to induce cancer-related inflammation in glioblastoma.The EMBO journal · 2023Article
- Weak UVB Irradiation Promotes Macrophage M2 Polarization and Stabilizes Atherosclerosis.Journal of cardiovascular translational research · 2022Article
- Activation of the JNKs/ATM-p53 axis is indispensable for the cytoprotection of dermal fibroblasts exposed to UVB radiation.Cell death & disease · 2022Article
- Tideglusib promotes wound healing in aged skin by activating PI3K/Akt pathway.Stem cell research & therapy · 2022Article
- Molecular regulation of lifespan extension in fertile ant workers.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2021Article
- Review
- Dual inhibition of DNA-PKcs and mTOR by CC-115 potently inhibits human renal cell carcinoma cell growth.Aging · 2020Article
- Review
- Association of the Epithelial-Mesenchymal Transition (EMT) with Cisplatin Resistance.International journal of molecular sciences · 2020Review
- Aspirin enhances cisplatin sensitivity of resistant non-small cell lung carcinoma stem-like cells by targeting mTOR-Akt axis to repress migration.Scientific reports · 2019Article
- DNA‑PKcs inhibitor increases the sensitivity of gastric cancer cells to radiotherapy.Oncology reports · 2019Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe exposure of skin keratinocytes to Ultraviolet (UV) irradiation leads to Akt phosphorylation at Ser-473, which is important for the carcinogenic effects of excessive sun exposure. The present study investigated the underlying mechanism of Akt Ser-473 phosphorylation by UVB radiation.
resultsWe found that DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and mammalian target of rapamycin (mTOR) complex 2 (mTORC2) were both required for UVB-induced Akt Ser-473 phosphorylation in keratinocytes. Inhibition of DNA-PKcs activity via its inhibitor NU7026, a dominant-negative kinase-dead mutation, RNA interference (RNAi) or gene depletion led to the attenuation of UVB-induced Akt Ser-473 phosphorylation. Meanwhile, siRNA silencing or gene depletion of SIN1, a key component of mTORC2, abolished Akt Ser-473 phosphorylation by UVB. Significantly, we discovered that DNA-PKcs was associated with SIN1 in cytosol upon UVB radiation, and this complexation appeared required for Akt Ser-473 phosphorylation. Meanwhile, this DNA-PKcs-SIN1 complexation by UVB was dependent on epidermal growth factor receptor (EGFR) activation, and was disrupted by an EGFR inhibitor (AG1478) or by EGFR depletion. UVB-induced complexation between DNA-PKcs and mTORC2 components was also abolished by NU7026 and DNA-PKcs mutation. Finally, we found that both DNA-PKcs and SIN1 were associated with apoptosis resistance of UVB radiation, and inhibition of them by NU7026 or genetic depletion significantly enhanced UVB-induced cell death and apoptosis.
conclusionTaken together, these results strongly suggest that DNA-PKcs-mTORC2 association is required for UVB-induced Akt Ser-473 phosphorylation and cell survival, and might be important for tumor cell transformation.
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