ArticleMolecular cancer therapeutics2015
CDK1-Mediated SIRT3 Activation Enhances Mitochondrial Function and Tumor Radioresistance.
Article in Molecular cancer therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 93 citations in OpenAlex.
- Apigenin Protects Against Cisplatin-Induced Cardiotoxicity: Potential Involvement of CD38-Sirt3 Signaling in Rats.Molecules (Basel, Switzerland) · 2026Article
- Oncogenic GPRIN1 sustains proliferation and mitochondrial homeostasis via dual‑layer CDK1-PI3K/Akt signalling in gallbladder cancer.Cell death & disease · 2026Article
- CHK1 as a Metabolic and Immunological Regulator: Implications for Cancer Therapy.Oncology research · 2026Review
- Multi-omics analysis identifies CCNB1 as a cell cycle factor driving glioblastoma progression and its inhibition by resveratrol.PloS one · 2026Article
- Sirtuins in Central Nervous System Tumors-Molecular Mechanisms and Therapeutic Targeting.Cells · 2025Review
- Regulation of cellular senescence in tumor progression and therapeutic targeting: mechanisms and pathways.Molecular cancer · 2025Review
- The study on the role of O-GlcNAcylation of SIRT3 in regulating mitochondrial oxidative stress during simulate myocardial ischemia-reperfusion.Scientific reports · 2024Article
- Palmitoyl-L-carnitine induces tau phosphorylation and mitochondrial dysfunction in neuronal cells.PloS one · 2024Article
- SIRT3-dependent mitochondrial redox homeostasis mitigates CHK1 inhibition combined with gemcitabine treatment induced cardiotoxicity in hiPSC-CMs and mice.Archives of toxicology · 2023Article
- The Cyclin-dependent kinase 1: more than a cell cycle regulator.British journal of cancer · 2023Review
- Mitochondrial metabolism: a predictive biomarker of radiotherapy efficacy and toxicity.Journal of cancer research and clinical oncology · 2023Review
- Targeting CDK1 in cancer: mechanisms and implications.NPJ precision oncology · 2023Review
- Tumor metabolism rewiring in epithelial ovarian cancer.Journal of ovarian research · 2023Review
- Sirtuins at the Crossroads between Mitochondrial Quality Control and Neurodegenerative Diseases: Structure, Regulation, Modifications, and Modulators.Aging and disease · 2023Review
- Exploring the pathogenesis of colorectal carcinoma complicated with hepatocellular carcinoma via microarray data analysis.Frontiers in pharmacology · 2023Article
- Review of possible mechanisms of radiotherapy resistance in cervical cancer.Frontiers in oncology · 2023Review
- The sirtuin family in health and disease.Signal transduction and targeted therapy · 2022Review
- USP14 regulates cell cycle progression through deubiquitinating CDK1 in breast cancer.Acta biochimica et biophysica Sinica · 2022Article
- The Plasma Proteome Fingerprint Associated with Circulating Carotenoids and Retinol in Older Adults.The Journal of nutrition · 2022Article
- Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Tumor adaptive resistance to therapeutic radiation remains a barrier for further improvement of local cancer control. SIRT3, a member of the sirtuin family of NAD(+)-dependent protein deacetylases in mitochondria, promotes metabolic homeostasis through regulation of mitochondrial protein deacetylation and plays a key role in prevention of cell aging. Here, we demonstrate that SIRT3 expression is induced in an array of radiation-treated human tumor cells and their corresponding xenograft tumors, including colon cancer HCT-116, glioblastoma U87, and breast cancer MDA-MB231 cells. SIRT3 transcriptional activation is due to SIRT3 promoter activation controlled by the stress transcription factor NF-κB. Posttranscriptionally, SIRT3 enzymatic activity is further enhanced via Thr150/Ser159 phosphorylation by cyclin B1-CDK1, which is also induced by radiation and relocated to mitochondria together with SIRT3. Cells expressing Thr150Ala/Ser159Ala-mutant SIRT3 show a reduction in mitochondrial protein lysine deacetylation, Δψm, MnSOD activity, and mitochondrial ATP generation. The clonogenicity of Thr150Ala/Ser159Ala-mutant transfectants is lower and significantly decreased under radiation. Tumors harboring Thr150Ala/Ser159Ala-mutant SIRT3 show inhibited growth and increased sensitivity to in vivo local irradiation. These results demonstrate that enhanced SIRT3 transcription and posttranslational modifications in mitochondria contribute to adaptive radioresistance in tumor cells. CDK1-mediated SIRT3 phosphorylation is a potential effective target to sensitize tumor cells to radiotherapy.
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