ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
The E3 Ligase TRIM4 Facilitates SET Ubiquitin-Mediated Degradation to Enhance ER-α Action in Breast Cancer.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. 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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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- TRIM Protein Superfamily in Breast Cancer: Yin and Yang.Biochemical genetics · 2026Review
- Protein modification systems as cancer biomarkers and therapeutic targets.Precision clinical medicine · 2026Review
- Senescent endothelial cell-derived extracellular vesicles promote neoadjuvant chemoresistance in colorectal cancer via GPX4.Communications biology · 2026Article
- Trim15 stabilizes VDAC3 via ubiquitination to suppress autophagy and enhance chemosensitivity in hypopharyngeal squamous cell carcinoma.Cell death discovery · 2026Article
- Tobacco Smoking Rewires Cell Metabolism by Inducing GAPDH Succinylation to Promote Lung Cancer Progression.Cancer research · 2025Article
- Hypoxia-triggered ERRα acetylation enhanced its oncogenic role and promoted progression of renal cell carcinoma by coordinating autophagosome-lysosome fusion.Cell death & disease · 2025Article
- Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities.Cells · 2025Review
- Association of Proteasome Activity and Pool Heterogeneity with Markers Determining the Molecular Subtypes of Breast Cancer.Cancers · 2025Article
- SET facilitates immune escape of microsatellite stability colorectal cancer by inhibiting c-Myc degradation.Cancer science · 2025Article
- Multifaceted role ofMedComm · 2024Review
- Article
- Trim21-mediated CCT2 ubiquitination suppresses malignant progression and promotes CD4Cell death & disease · 2024Article
- The next decade of SET: from an oncoprotein to beyond.Journal of molecular cell biology · 2024Review
- Emerging roles of tripartite motif family proteins (TRIMs) in breast cancer.Cancer medicine · 2024Review
- A multi-tissue, splicing-based joint transcriptome-wide association study identifies susceptibility genes for breast cancer.American journal of human genetics · 2024Article
- Article
- TRIM4 enhances small-molecule-induced neddylated-degradation of CORO1A for triple negative breast cancer therapy.Theranostics · 2024Article
- The E3 Ligase TRIM4 Facilitates SET Ubiquitin-Mediated Degradation to Enhance ER-α Action in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Estrogen receptor alpha (ER-α) action is critical for hormone-dependent breast cancer, and ER-α dysregulation can lead to the emergence of resistance to endocrine therapy. Here, it is found that TRIM4 is downregulated in tamoxifen (TAM)-resistant breast cancer cells, while the loss of TRIM4 is associated with an unfavorable prognosis. In vitro and in vivo experiments confirm that TRIM4 increased ER-α expression and the sensitivity of breast cancer cells to TAM. Mechanistically, TRIM4 is found to target SET, and TRIM4-SET interactions are mediated by the RING and B-box domains of TRIM4 and the carboxyl terminus of SET. Moreover, it is determined that TRIM4 catalyzed the K48-linked polyubiquitination of SET (K150 and K172), promoting its proteasomal degradation and disassociation from p53 and PP2A. Once released, p53 and PP2A are able to further promote ESR1 gene transcription and enhance mRNA stability. Moreover, univariate and multivariate Cox proportional hazards regression analyses confirm that TRIM4 expression is an independent predictor of overall survival and recurrence-free survival outcomes in patients with ER-α positive breast cancer. Taken together, the data highlights a previously undiscovered mechanism and suggest that TRIM4 is a valuable biomarker that can be analyzed to predict response to endocrine therapy in breast cancer patients.
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