ArticleCell death & disease2020
Induction of NEDD8-conjugating enzyme E2 UBE2F by platinum protects lung cancer cells from apoptosis and confers to platinum-insensitivity.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- The UBE2/E2 ubiquitin-conjugating enzyme family at the interface of tumor biology and antitumor immunity: mechanisms, biomarkers, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Progression on Mechanism and Therapeutic Implications of Neddylation in Lung Cancer.Oncology research · 2026Review
- Ubiquitin-conjugating Enzymes in Cancer.International journal of biological sciences · 2026Review
- Integrated single-cell and bulk transcriptomic analyses reveal cDC1-centered ubiquitination dysregulation and identify UBE2F as a critical regulator in sepsis.Frontiers in immunology · 2026Article
- The role of neddylation in colorectal cancer and its therapeutic potential.Discover oncology · 2025Review
- Deciphering the roles of neddylation modification in hepatocellular carcinoma: Molecular mechanisms and targeted therapeutics.Genes & diseases · 2025Review
- Article
- UBE2M forms a positive feedback loop with estrogen receptor to drive breast cancer progression and drug resistance.Cell death & disease · 2024Article
- Advances of E3 ligases in lung cancer.Biochemistry and biophysics reports · 2024Review
- Discovery of neddylation E2s inhibitors with therapeutic activity.Oncogenesis · 2023Review
- Targeting neddylation as a novel approach to lung cancer treatment (Review).International journal of oncology · 2023Review
- NEDD8-conjugating enzyme E2s: critical targets for cancer therapy.Cell death discovery · 2023Review
- Targeting cullin neddylation for cancer and fibrotic diseases.Theranostics · 2023Review
- Article
- NEDD8-conjugating enzyme E2 UBE2F confers radiation resistance by protecting lung cancer cells from apoptosis.Journal of Zhejiang University. Science. B · 2021Article
- A polydopamine nanomedicine used in photothermal therapy for liver cancer knocks down the anti-cancer target NEDD8-E3 ligase ROC1 (RBX1).Journal of nanobiotechnology · 2021Article
- Ubiquitin-Conjugating Enzymes in Cancer.Cells · 2021Review
- Review
- Targeting neddylation E2s: a novel therapeutic strategy in cancer.Journal of hematology & oncology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Platinum is a widely used first-line chemotherapy in treating non-small cell lung cancer of adenocarcinoma. Unfortunately, platinum resistance leads to relapse and therapeutic failure, enabling the development of platinum-sensitization strategies to be of great clinical significance. Here, we report that the upregulation of the NEDD8-conjugating enzyme UBE2F is an important way for lung cancer cells to escape platinum-induced cell apoptosis, which confers to insensitivity to platinum-based chemotherapy. Mechanistically, platinum treatment impairs the complex formation for proteasome-mediated UBE2F degradation, evidenced by the weaker association between UBE2F and Ring-box protein 1 (RBX1), an essential component of Cullin-Ring E3 ligases (CRLs), thus leading to the accumulation of UBE2F. The accumulated UBE2F promotes the neddylation levels and activity of Cullin5, in accord with the lower expression of pro-apoptotic protein NOXA, a well-known substrate of Cullin-Ring E3 ligase 5 (CRL5). Additionally, knockout of UBE2F significantly sensitizes lung cancer cells to platinum treatment by enhancing the protein levels of NOXA and subsequently promoting cell apoptosis. Our observations uncover a previously unknown regulatory mechanism of UBE2F stability upon platinum chemotherapy and suggest that UBE2F might be a novel therapy target for sensitizing lung cancer cells to platinum-based chemotherapy.
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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.