ArticleThe Journal of biological chemistry2012
Overexpression of SKI oncoprotein leads to p53 degradation through regulation of MDM2 protein sumoylation.
Article in The Journal of biological chemistry, 2012. 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Unraveling the critical role of SUMOylation in the governing of tumor immunity.Frontiers in immunology · 2025Review
- Development of dual aptamers-functionalized c-MET PROTAC degraders for targeted therapy of osteosarcoma.Theranostics · 2025Article
- The SUMOylation and ubiquitination crosstalk in cancer.Journal of cancer research and clinical oncology · 2023Review
- TAK-981, a SUMOylation inhibitor, suppresses AML growth immune-independently.Blood advances · 2023Article
- Cancer-Associated Dysregulation of Sumo Regulators: Proteases and Ligases.International journal of molecular sciences · 2022Review
- SUMOylation and NEDDylation in Primary and Metastatic Cancers to Bone.Frontiers in cell and developmental biology · 2022Review
- Novel insights into the impact of the SUMOylation pathway in hematological malignancies (Review).International journal of oncology · 2021Review
- Expression and Prognosis Analysis of SUMOylation Regulators in Oral Squamous Cell Carcinoma Based on High-Throughput Sequencing.Frontiers in genetics · 2021Article
- The Function of SUMOylation and Its Role in the Development of Cancer Cells under Stress Conditions: A Systematic Review.Stem cells international · 2020Review
- SUMOylation in Glioblastoma: A Novel Therapeutic Target.International journal of molecular sciences · 2019Review
- Hypoxia-inducible factor 1α (HIF-1α) mediates the epithelial-mesenchymal transition in benign prostatic hyperplasia.International journal of clinical and experimental pathology · 2019Article
- SUMOylation and phosphorylation cross-talk in hepatocellular carcinoma.Translational gastroenterology and hepatology · 2018Review
- SUMO and the robustness of cancer.Nature reviews. Cancer · 2017Review
- Regulation of epithelial-mesenchymal transition through SUMOylation of transcription factors.Cancer research · 2015Review
- Targeting MDM2-p53 interaction for cancer therapy: are we there yet?Current medicinal chemistry · 2014Review
- c-Ski activates cancer-associated fibroblasts to regulate breast cancer cell invasion.Molecular oncology · 2013Article
- Article
- Transcriptional cofactors Ski and SnoN are major regulators of the TGF-β/Smad signaling pathway in health and disease.Signal transduction and targeted therapyArticle
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Protooncogene Ski was identified based on its ability to transform avian fibroblasts in vitro. In support of its oncogenic activity, SKI was found to be overexpressed in a variety of human cancers, although the exact molecular mechanism(s) responsible for its oncogenic activity is not fully understood. We found that SKI can negatively regulate p53 by decreasing its level through up-regulation of MDM2 activity, which is mediated by the ability of SKI to enhance sumoylation of MDM2. This stimulation of MDM2 sumoylation is accomplished through a direct interaction of SKI with SUMO-conjugating enzyme E2, Ubc9, resulting in enhanced thioester bond formation and mono-sumoylation of Ubc9. A mutant SKI defective in transformation fails to increase p53 ubiquitination and is unable to increase MDM2 levels and to increase mono-sumoylation of Ubc9, suggesting that the ability of SKI to enhance Ubc9 activity is essential for its transforming function. These results established a detailed molecular mechanism that underlies the ability of SKI to cause cellular transformation while unraveling a novel connection between sumoylation and tumorigenesis, providing potential new therapeutic targets for cancer.
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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.