ArticleCell death & disease2022
The RBPJ/DAPK3/UBE3A signaling axis induces PBRM1 degradation to modulate the sensitivity of renal cell carcinoma to CDK4/6 inhibitors.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 15 citations in OpenAlex.
- UBE3A-mediated mH2A1 Ubiquitination activates TERT transcription to promote senescence resistance in pancreatic cancer.Cell death & disease · 2026Article
- The expression, regulation, and function of human endogenous retroviruses in genitourinary cancers.Cell death discovery · 2025Review
- UBE3A promotes foam cell formation and counters remyelination by targeting ABCA1 for proteasomal degradation.Nature communications · 2025Article
- The Transcription Factor CREB1 Triggers the Progression of Clear Cell Renal Cell Carcinoma by Promoting CENPE Expression.Journal of cellular and molecular medicine · 2025Article
- SOX11 exacerbates ferroptosis to reduce lenvatinib resistance in liver cancer cells by promoting ubiquitination degradation of SREBF1 through upregulating UBE3A.Molecular and cellular biochemistry · 2025Article
- Loss of UBE3A impacts both neuronal and non-neuronal cells in human cerebral organoids.Communications biology · 2025Article
- DAPK3 is Essential for DBP-Induced Autophagy of Mouse Leydig Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Chromatin remodeling and cancer: the critical influence of the SWI/SNF complex.Epigenetics & chromatin · 2025Review
- Neuronal UBE3A substrates hold therapeutic potential for Angelman syndrome.Current opinion in neurobiology · 2024Review
- PBRM1 presents a potential ctDNA marker to monitor response to neoadjuvant chemotherapy in cervical cancer.iScience · 2024Article
- Tumor-associated macrophage-derived exosomes LINC01592 induce the immune escape of esophageal cancer by decreasing MHC-I surface expression.Journal of experimental & clinical cancer research : CR · 2023Article
- Essential role of bromodomain proteins in renal cell carcinoma (Review).Molecular medicine reports · 2023Review
- MicroRNA-375 restrains the progression of lung squamous cell carcinoma by modulating the ERK pathway via UBE3A-mediated DUSP1 degradation.Cell death discovery · 2023Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal cell carcinoma (RCC) is a kind of malignant tumor originating from the renal tubular epithelium. Approximately 30% of patients with renal cancer are found to have metastasis when first diagnosed. Exploring other effective treatment methods in addition to surgery is an urgent need in the research field of renal cell carcinoma. Polybromo 1 (PBRM1) is the second most mutated gene in RCC, with a mutation rate of ~40%. Notably, the posttranscriptional modification of PBRM1 in RCC is unclear. In this study, we performed unbiased mass spectrometry of PBRM1 and identified ubiquitin-protein ligase E3A (UBE3A), an extensively studied E3 ligase that can bind with PBRM1 and regulate the stability of PBRM1 in renal cancer cells. We further found that RBPJ/DAPK3 modulated the E3 ligase activity of UBE3A by interfering with the PKA phosphorylation of UBE3A. Finally, we demonstrated that the RBPJ/DAPK3/UBE3A/PBRM1/p21 axis contributed to the sensitivity of renal cancer cells to CDK4/6 inhibitors. In addition, in combination with RBPJ inhibitors, CDK4/6 inhibitors showed synergistically enhanced effects on renal cancer cells. In summary, we not only revealed a novel RBPJ/DAPK3/UBE3A/PBRM1/p21 signaling axis but also identified a combination strategy for overcoming the resistance of renal cancer cells to CDK4/6 inhibitors.
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