ArticleInternational journal of biological sciences2023
Neddylation of HER2 Inhibits its Protein Degradation and promotes Breast Cancer Progression.
Article in International journal of biological sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 21 citations in OpenAlex.
- Endothelial deletion of the neddylation E2 enzyme UBE2M inhibits tumor growth by promoting nonproductive angiogenesis.The Journal of clinical investigation · 2026Article
- Protein neddylation as a therapeutic target: challenges and opportunities.The Journal of clinical investigation · 2026Review
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- CAND1 mediates CUL7-dependent HER2 protein stability to drive breast cancer progression.Breast cancer research : BCR · 2025Article
- The deubiquitinase USP7 stabilizes HER2 expression and promotes breast cancer progression.Neoplasia (New York, N.Y.) · 2025Article
- Comprehensive analysis Neddylation-related genes identified UBB as a prognostic biomarker for clear cell renal cell carcinoma.Discover oncology · 2025Article
- Inhibiting neddylation: A new strategy for tumor therapy.Journal of pharmaceutical analysis · 2025Review
- Pan-cancer analysis unveils the role and mechanisms of neddylation modifications in tumorigenesis.Medical oncology (Northwood, London, England) · 2025Article
- Comparative bioinformatics analysis of the Wnt pathway in breast cancer: Selection of novel biomarker panels associated with ER status.Open life sciences · 2025Article
- SENP3 mediates deSUMOylation of SIX1 to promote prostate cancer proliferation and migration.Cellular & molecular biology letters · 2024Article
- Neddylation steers the fate of cellular receptors.Experimental & molecular medicine · 2024Review
- Bio-Pathological Functions of Posttranslational Modifications of Histological Biomarkers in Breast Cancer.Molecules (Basel, Switzerland) · 2024Review
- UBE2M forms a positive feedback loop with estrogen receptor to drive breast cancer progression and drug resistance.Cell death & disease · 2024Article
- The Double-Edged Effects of MLN4924: Rethinking Anti-Cancer Drugs Targeting the Neddylation Pathway.Biomolecules · 2024Review
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Exploring the Role of Unconventional Post-Translational Modifications in Cancer Diagnostics and Therapy.Current protein & peptide science · 2024Review
- Association between the systemic immune-inflammation index and the efficacy of neoadjuvant chemotherapy, prognosis in HER2 positive breast cancer-a retrospective cohort study.Gland surgery · 2023Article
- HER2-Low Breast Cancer: Current Landscape and Future Prospects.Breast cancer (Dove Medical Press) · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HER2 is a transmembrane receptor with intrinsic tyrosine kinase activity that is overexpressed in almost 25% of human breast cancers. Here, we report that the neddylation of HER2 is a new post-translational modification that controls its expression and oncogenic activity in human breast cancer. Two critical members in the neddylation pathway, NEDD8 and NEDD8-activating enzyme E1 subunit 1 (NAE1), are detected in human breast specimens. Overexpressed NEDD8 and NAE1 are positively correlated with HER2 expression in human breast cancer. Subsequent structure and function experiments show that HER2 directly interacts with NEDD8 and NAE1, whereas HER2 protein expression is decreased by neddylation depletion. Mechanistically, neddylation inhibition promotes the degradation of HER2 protein by improving its ubiquitination. HER2 overexpression abrogates neddylation depletion-triggered cell growth suppression. The inhibition of neddylation synergized with trastuzumab significantly suppresses growth of HER2 positive breast cancer. Collectively, this study demonstrates a previously undiscovered role of NEDD8-dependent HER2 neddylation promotes tumor growth in breast 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.