ArticleCell death and differentiation2013
The histone deacetylase SIRT2 stabilizes Myc oncoproteins.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers.
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Who cites it
132 citing papers in PubMed, 203 citations in OpenAlex.
- Sirtuins in Medicine: Multifaceted Roles in Physiological Processes and Cardiovascular Diseases.Biomolecules · 2026Review
- Structure-Guided Optimization and Biological Validation of 1,3,4-Thiadiazole-Based SIRT2 Inhibitors Reinforcing Channel Entrance Interactions.Drug development research · 2026Article
- Inhibition of ZBTB7B-mediated ADPGK transcription by NEDD4 impedes glycolysis and progression of lung adenocarcinoma.Oncogenesis · 2026Article
- Article
- Iron regulation by Sirtuins 1 & 2 and their therapeutic modulation by Sirtinol.Frontiers in pharmacology · 2026Review
- The Yin-Yang balance of SIRT1 and SIRT2 in cancer metabolic remodeling.International journal of biological sciences · 2026Review
- Expression and clinical significance of SIRT2 in gastric cancer: a retrospective study.Annals of medicine and surgery (2012) · 2025Article
- Research advancements regarding the relationship between FBXO2 and malignant tumors (Review).Molecular medicine reports · 2025Review
- Comprehensive analysis of the role of NEDD4 in pan-cancer and experimental verification of its role in KIRC progression.Discover oncology · 2025Article
- SIRT2 Regulates the SMARCB1 Loss-Driven Differentiation Block in ATRT.Molecular cancer research : MCR · 2025Article
- The Co-Delivery of Natural Products and Small RNAs for Cancer Therapy: A Review.Molecules (Basel, Switzerland) · 2025Review
- Emerging frontiers in epigenetic-targeted therapeutics for pediatric neuroblastoma.Frontiers in immunology · 2025Review
- Sirtuins as Key Regulators in Pancreatic Cancer: Insights into Signaling Mechanisms and Therapeutic Implications.Cancers · 2024Review
- Golgi-localized Ring Finger Protein 121 is necessary for MYCN-driven neuroblastoma tumorigenesis.Communications biology · 2024Article
- Review
- Screening approach by a combination of computational and in vitro experiments: identification of fluvastatin sodium as a potential SIRT2 inhibitor.Journal of molecular modeling · 2024Article
- SIRT2 promotes base excision repair by transcriptionally activating OGG1 in an ATM/ATR-dependent manner.Nucleic acids research · 2024Article
- Sirt2 inhibition improves gut epithelial barrier integrity and protects mice from colitis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A molecular circuit linking the BCR to the NAD biosynthetic enzyme NAMPT is an actionable target in Richter syndrome.Blood advances · 2024Article
- The mechanosensitive geneAmerican journal of physiology. Cell physiology · 2024Article
72 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Myc oncoproteins are commonly upregulated in human cancers of different organ origins, stabilized by Aurora A, degraded through ubiquitin-proteasome pathway-mediated proteolysis, and exert oncogenic effects by modulating gene and protein expression. Histone deacetylases are emerging as targets for cancer therapy. Here we demonstrated that the class III histone deacetylase SIRT2 was upregulated by N-Myc in neuroblastoma cells and by c-Myc in pancreatic cancer cells, and that SIRT2 enhanced N-Myc and c-Myc protein stability and promoted cancer cell proliferation. Affymetrix gene array studies revealed that the gene most significantly repressed by SIRT2 was the ubiquitin-protein ligase NEDD4. Consistent with this finding, SIRT2 repressed NEDD4 gene expression by directly binding to the NEDD4 gene core promoter and deacetylating histone H4 lysine 16. Importantly, NEDD4 directly bound to Myc oncoproteins and targeted Myc oncoproteins for ubiquitination and degradation, and small-molecule SIRT2 inhibitors reactivated NEDD4 gene expression, reduced N-Myc and c-Myc protein expression, and suppressed neuroblastoma and pancreatic cancer cell proliferation. Additionally, SIRT2 upregulated and small-molecule SIRT2 inhibitors decreased Aurora A expression. Our data reveal a novel pathway critical for Myc oncoprotein stability, and provide important evidences for potential application of SIRT2 inhibitors for the prevention and therapy of Myc-induced malignancies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.