ArticleOncoTargets and therapy2019
NEDD4 Negatively Regulates GITR via Ubiquitination in Immune Microenvironment of Melanoma.
Article in OncoTargets and therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Network-based analysis reveals potential microRNA regulation of oncogenic pathways in SOX10-depleted uveal melanoma.Cellular and molecular life sciences : CMLS · 2026Article
- Plasma protein levels and hepatocellular carcinoma: a Mendelian randomization study with drug screening implications.Discover oncology · 2025Article
- Article
- The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy.Frontiers in immunology · 2023Review
- Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.International journal of molecular sciences · 2022Review
- Development and validation of a novel ubiquitination-related gene prognostic signature based on tumor microenvironment for colon cancer.Translational cancer research · 2022Article
- Roles of ubiquitination in the crosstalk between tumors and the tumor microenvironment (Review).International journal of oncology · 2022Review
- The Interplay between Tumour Microenvironment Components in Malignant Melanoma.Medicina (Kaunas, Lithuania) · 2022Review
- NEDD4 E3 ubiquitin protein ligase serves an important role in cutaneous melanoma occurrence and development.Experimental and therapeutic medicine · 2021Article
- Ubiquitination in T-Cell Activation and Checkpoint Inhibition: New Avenues for Targeted Cancer Immunotherapy.International journal of molecular sciences · 2021Review
- Targeting ubiquitin signaling for cancer immunotherapy.Signal transduction and targeted therapy · 2021Review
- FKBP51 Affects TNF-Related Apoptosis Inducing Ligand Response in Melanoma.Frontiers in cell and developmental biology · 2021Article
- The Influence of Tumor Microenvironment on Immune Escape of Melanoma.International journal of molecular sciences · 2020Review
- A novel predictive model incorporating immune-related gene signatures for overall survival in melanoma patients.Scientific reports · 2020Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionMelanoma is a common skin cancer that is usually associated with poor clinical outcomes. Recently, the immune checkpoint GITR has been identified as a promising target for immunotherapy of melanoma. In this study, we aimed to investigate the post-translational regulation mechanism of GITR in melanoma.
methodsWestern blotting was used to evaluate the protein expression of NEDD4, GITR and Foxp3. Real-time PCR (RT-PCR) was performed to determine expression levels of NEDD4, GITR, Foxp3 and IL-2. Cell viability was detected by MTT assay. The ubiquitination of GITR was evaluated by immunoprecipitation. NEDD4 expression data and melanoma survival data were obtained from The Cancer Genome Atlas (TCGA) and cBioPortal databases.
resultsWe demonstrate that E3 ligase NEDD4 binds to GITR and mediates ubiquitination and degradation of GITR. Overexpression of NEDD4 inhibits anti-tumor immunity mediated by T cells against melanoma cells. We also found that the expression of NEDD4 is increased in metastatic melanoma. High NEDD4 expression level is correlated with the poor prognosis of melanoma patients. DISCUSSION: In summary, our findings demonstrated that E3 ligase NEDD4 mediates ubiquitination and degradation of GITR and suppresses T-cell-mediated-killings on melanoma cells. Our work highlighted the E3 ligase NEDD4 as a novel prognosis biomarker and therapeutic target for melanoma.
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