ArticleNucleic acids research2016
SOX9 is targeted for proteasomal degradation by the E3 ligase FBW7 in response to DNA damage.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 62 citations in OpenAlex.
- dubTAGs enable on-demand stabilization for tunable and reversible control of endogenous protein levels.bioRxiv : the preprint server for biology · 2026Article
- SOX10-mediated regulation of the MiR-106a/363 cluster drives RAF inhibitor resistance in BRAF-mutant melanoma.Cellular and molecular life sciences : CMLS · 2026Article
- Targeting APE1-Redox Function Reverses SOX9-mediated Chemoresistance in Esophageal Adenocarcinoma.Gastroenterology · 2026Article
- Methodological Landscape of DNA Damage Response Detection: From Conventional Assays to Future Innovations.Current issues in molecular biology · 2026Review
- Intrinsic mechanisms and microenvironmental cues fine-tune plasticity of esophageal progenitors.Nature communications · 2026Article
- Protein arginine methyltransferase 7-mediated arginine mono-methylation stabilizes SRY-box transcription factor 9 to promote non-small cell lung cancer progression.Molecular biomedicine · 2025Article
- Characterization of quiescent subpopulations and proliferative compartments in glioblastoma.bioRxiv : the preprint server for biology · 2025Article
- USP18 deubiquitinates and stabilizes SOX9 to promote the stemness and malignant progression of glioblastoma.Cell death discovery · 2025Article
- USP28 promotes PARP inhibitor resistance by enhancing SOX9-mediated DNA damage repair in ovarian cancer.Cell death & disease · 2025Article
- Variants in the SOX9 transactivation middle domain induce axial skeleton dysplasia and scoliosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- F-box proteins at the crossroads of ubiquitination and tumor immunity: regulatory networks and immunotherapy strategies.Frontiers in immunology · 2025Review
- LncRNA-Mediated TPI1 and PKM2 Promote Self-Renewal and Chemoresistance in GBM.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Molecular insights and clinical implications for the tumor suppressor role of SCFBiochimica et biophysica acta. Reviews on cancer · 2024Review
- FBXW7-loss Sensitizes Cells to ATR Inhibition Through Induced Mitotic Catastrophe.Cancer research communications · 2023Article
- The role of E3 ubiquitin ligases in bone homeostasis and related diseases.Acta pharmaceutica Sinica. B · 2023Review
- A Novel Mouse Model of Combined Hepatocellular-Cholangiocarcinoma Induced by Diethylnitrosamine and Loss ofCancers · 2023Article
- Lysine 68 Methylation-Dependent SOX9 Stability Control Modulates Chondrogenic Differentiation in Dental Pulp Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- SOX9 drives KRAS-induced lung adenocarcinoma progression and suppresses anti-tumor immunity.Oncogene · 2023Article
- Ubiquitination Links DNA Damage and Repair Signaling to Cancer Metabolism.International journal of molecular sciences · 2023Review
- Cisplatin-induced cell death increases the degradation of the MRE11-RAD50-NBS1 complex through the autophagy/lysosomal pathway.Cell death and differentiation · 2023Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
SOX9 encodes a transcription factor that governs cell fate specification throughout development and tissue homeostasis. Elevated SOX9 is implicated in the genesis and progression of human tumors by increasing cell proliferation and epithelial-mesenchymal transition. We found that in response to UV irradiation or genotoxic chemotherapeutics, SOX9 is actively degraded in various cancer types and in normal epithelial cells, through a pathway independent of p53, ATM, ATR and DNA-PK. SOX9 is phosphorylated by GSK3β, facilitating the binding of SOX9 to the F-box protein FBW7α, an E3 ligase that functions in the DNA damage response pathway. The binding of FBW7α to the SOX9 K2 domain at T236-T240 targets SOX9 for subsequent ubiquitination and proteasomal destruction. Exogenous overexpression of SOX9 after genotoxic stress increases cell survival. Our findings reveal a novel regulatory mechanism for SOX9 stability and uncover a unique function of SOX9 in the cellular response to DNA damage. This new mechanism underlying a FBW7-SOX9 axis in cancer could have implications in therapy resistance.
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Registered trials
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.