ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
RNF126-Mediated MRE11 Ubiquitination Activates the DNA Damage Response and Confers Resistance of Triple-Negative Breast Cancer to Radiotherapy.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 58 citations in OpenAlex.
- Targeting E3 ubiquitin ligases: Mechanistic breakthroughs and novel clinical translation pathways for tumor radioimmunotherapy.Molecular cancer · 2026Review
- Review
- RNF126 mediates fetal growth restriction via ubiquitination-dependent degradation of the MYH9/MYH10 complex.iScience · 2026Article
- An HDAC4-specific PROTAC degrader achieves radiation sensitization by enhancing ferroptosis in lung cancer.Nature communications · 2026Article
- USP18 promotes nasopharyngeal carcinoma radioresistance via TRIM29 oligomerization and ubiquitination.Cell death and differentiation · 2026Article
- Therapeutic Mechanisms of Stem Cell-Derived Exosomes for Neurological Disorders: An Overview.Molecular neurobiology · 2026Review
- SIRT5-RNF126 coordinated regulation of METTL17 stability controls mitochondrial function and glioma progression.Cell & bioscience · 2026Article
- The Therapeutic Potential of Dihydroartemisinin in Cancer Treatment.International journal of molecular sciences · 2026Review
- TONSL promotes hepatocellular carcinoma progression and radioresistance by orchestrating DNA damage repair and cell cycle dynamics.Discover oncology · 2026Article
- YEATS2 promotes DNA repair and induces anoikis resistance by enhancing chromatin accessibility to drive prostate cancer metastasis.Oncogene · 2026Article
- PRDM1 restricts bladder cancer progression and enhances chemosensitivity by suppressing OTUD6A-mediated deubiquitination of CDC6.Cell death & disease · 2026Article
- Tumor cell cycle regulation: integrated perspective of stage characteristics, regulatory networks, and signaling pathway intervention strategies.Molecular biomedicine · 2026Review
- Breast cancer brain metastasis: from molecular insights to therapeutic innovation.Frontiers in immunology · 2026Review
- Radiation-induced nuclear translocation of NPRL2 hijacks E3 ubiquitin ligases to enhance DNA repairActa pharmaceutica Sinica. B · 2026Article
- Downregulation of ZFP36L1 contributes to methotrexate resistance in osteosarcoma through enhanced NHEJ DNA repair mechanisms.Cell death & disease · 2025Article
- ACOX2 destabilizes the MRE11-RAD50-NBS1 complex and boosts anticancer immunity via the cGAS-STING pathway in clear cell renal cell carcinoma.Molecular cancer · 2025Article
- Decoding the ubiquitin network: molecular mechanisms and therapeutic vulnerabilities for precision radio-sensitization in cancer.Molecular cancer · 2025Review
- C1orf116 inhibits acquired resistance to EGFR inhibitors in EGFR mutant lung adenocarcinoma by suppressing the ATM/ATR pathways.Translational lung cancer research · 2025Article
- A novel SWI/SNF complex promotes triple-negative breast cancer progression.Cellular & molecular biology letters · 2025Article
- Elucidating the dynamic tumor microenvironment through deep transcriptomic analysis and therapeutic implication of MRE11 expression patterns in hepatocellular carcinoma.Cancer cell international · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
22 authors at 7 institutions in 1 country.
Funding
Abstract
Triple-negative breast cancer (TNBC) has higher molecular heterogeneity and metastatic potential and the poorest prognosis. Because of limited therapeutics against TNBC, irradiation (IR) therapy is still a common treatment option for patients with lymph nodes or brain metastasis. Thus, it is urgent to develop strategies to enhance the sensitivity of TNBC tumors to low-dose IR. Here, the authors report that E3 ubiquitin ligase Ring finger protein 126 (RNF126) is important for IR-induced ATR-CHK1 pathway activation to enhance DNA damage repair (DDR). Mechanistically, RNF126 physically associates with the MRE11-RAD50-NBS1 (MRN) complex and ubiquitinates MRE11 at K339 and K480 to increase its DNA exonuclease activity, subsequent RPA binding, and ATR phosphorylation, promoting sustained DDR in a homologous recombination repair-prone manner. Accordingly, depletion of RNF126 leads to increased genomic instability and radiation sensitivity in both TNBC cells and mice. Furthermore, it is found that RNF126 expression is induced by IR activating the HER2-AKT-NF-κB pathway and targeting RNF126 expression with dihydroartemisinin significantly improves the sensitivity of TNBC tumors in the brain to IR treatment in vivo. Together, these results reveal that RNF126-mediated MRE11 ubiquitination is a critical regulator of the DDR, which provides a promising target for improving the sensitivity of TNBC to radiotherapy.
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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.