ArticleScience signaling2022
DNA-PK promotes activation of the survival kinase AKT in response to DNA damage through an mTORC2-ECT2 pathway.
Article in Science signaling, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Lipid transfer proteins and PI4KIIα initiate nuclear p53-phosphoinositide signaling.The Journal of biological chemistry · 2026Article
- The mTORC2 component SIN1 post-transcriptionally regulates TYMS levels and modulates P53 activity in response to 5-FU chemotherapy.Cell communication and signaling : CCS · 2026Article
- DNA sensors in metabolic and cardiovascular diseases: Molecular mechanisms and therapeutic prospects.Immunological reviews · 2025Review
- Disrupting resistance: novel therapeutic approaches to combat multidrug resistance in fusion-negative rhabdomyosarcoma.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- AKT kinases as therapeutic targets.Journal of experimental & clinical cancer research : CR · 2024Review
- GINS2 regulates temozolomide chemosensitivity via the EGR1/ECT2 axis in gliomas.Cell death & disease · 2024Article
- Statin-Sensitive Akt1/Src/Caveolin-1 Signaling Enhances Oxidative Stress Resistance in Rhabdomyosarcoma.Cancers · 2024Article
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- OiScience · 2024Article
- Key molecular DNA damage responses of human cells to radiation.Frontiers in cell and developmental biology · 2024Review
- Unmasking the tumourigenic role of SIN1/MAPKAP1 in the mTOR complex 2.Clinical and translational medicine · 2023Review
- Chemical inhibition of DNA-PKcs impairs the activation and cytotoxicity of CD4Immunology and cell biology · 2023Article
- Cytoplasmic DNA sensing boosts CD4Life medicine · 2023Article
- Arginine methylation of BRD4 by PRMT2/4 governs transcription and DNA repair.Science advances · 2022Article
- A p53-phosphoinositide signalosome regulates nuclear AKT activation.Nature cell biology · 2022Article
- Development and Evolution of DNA-Dependent Protein Kinase Inhibitors toward Cancer Therapy.International journal of molecular sciences · 2022Review
- The PIKK-AKT connection in the DNA damage response.Science signaling · 2022Article
- MicroRNAs in doxorubicin-induced cardiotoxicity: The DNA damage response.Frontiers in pharmacology · 2022Review
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Abstract
The kinase AKT (also known as protein kinase B) is a key regulator of cell proliferation, survival, and metabolism. In addition to being activated by growth factors, AKT is activated in response to DNA damage. Here, we found that the DNA damage response kinase DNA-PK sustains cell survival through a phosphorylation event that leads to increased AKT activity. In various cancer and noncancer cells in culture, DNA damage caused by ionizing radiation or topoisomerase inhibitors triggered DNA-PK–dependent phosphorylation of the mTOR complex 2 (mTORC2) subunit Sin1, which enabled its interaction with the guanine nucleotide exchange factor ECT2. Depleting Sin1 or ECT2 or disrupting the protein interaction or catalytic function of ECT2 attenuated DNA damage–induced AKT activation, thereby enhancing cellular sensitivity to DNA-damaging agents. Our findings elucidate a mechanism mediating DNA damage–induced AKT activation and cell survival.
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