ArticleMolecular cell2019
The F-Box Domain-Dependent Activity of EMI1 Regulates PARPi Sensitivity in Triple-Negative Breast Cancers.
Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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55 citing papers in PubMed, 72 citations in OpenAlex.
- FBXO5 regulates RPL23A to promote MDM2-mediated p53 degradation and facilitate malignant progression of breast cancer.Breast cancer research : BCR · 2026Article
- Translational prioritization of strategies to overcome poly ADP-ribose polymerase inhibitor resistance in breast cancer based on systematic review of preclinical evidence.Discover oncology · 2026Review
- Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.Pharmaceutics · 2026Review
- The expanding roles of homologous recombination proteins in genome stability.The EMBO journal · 2026Review
- Overcoming Resistance to PARP Inhibitors in BRCA-Mutated Cancers: Mechanisms and Therapeutic Strategies.Journal of Cancer · 2026Review
- The cytoskeletal protein smoothelin maintains homologous recombination repair by stabilizing RAD51 in an HUWE1-dependent manner in colorectal cancer.Acta pharmaceutica Sinica. B · 2025Article
- Prospects for PARG inhibitors in cancer therapy.Journal of molecular cell biology · 2025Review
- SOX5 inhibition overcomes PARP inhibitor resistance in BRCA-mutated breast and ovarian cancer.Cell death & disease · 2025Article
- SKP1-CUL1-F-box: Key molecular targets affecting disease progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Loss of EMI1 compromises chromosome stability and is associated with cellular transformation in colonic epithelial cell contexts.British journal of cancer · 2024Article
- APC/C prevents a noncanonical order of cyclin/CDK activity to maintain CDK4/6 inhibitor-induced arrest.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Effect of Emi1 gene silencing on the proliferation and invasion of human breast cancer cells.BMC molecular and cell biology · 2023Article
- Licochalcone A induces cell cycle arrest and apoptosis via suppressing MAPK signaling pathway and the expression of FBXO5 in lung squamous cell cancer.Oncology reports · 2023Article
- APC/C prevents non-canonical order of cyclin/CDK activity to maintain CDK4/6 inhibitor-induced arrest.bioRxiv : the preprint server for biology · 2023Article
- SCFNature communications · 2023Article
- Inhibition of CXorf56 promotes PARP inhibitor-induced cytotoxicity in triple-negative breast cancer.NPJ breast cancer · 2023Article
- PARP Inhibitors in Breast and Ovarian Cancer.Cancers · 2023Review
- Combined treatment of disulfiram with PARP inhibitors suppresses ovarian cancer.Frontiers in oncology · 2023Article
- FBXO5 acts as a novel prognostic biomarker for patients with cervical cancer.Frontiers in cell and developmental biology · 2023Article
- FBXW7 attenuates tumor drug resistance and enhances the efficacy of immunotherapy.Frontiers in oncology · 2023Review
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8 authors at 3 institutions in 1 country.
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Abstract
The BRCA1-BRCA2-RAD51 axis is essential for homologous recombination repair (HRR) and is frequently disrupted in breast cancers. PARP inhibitors (PARPis) are used clinically to treat BRCA-mutated breast tumors. Using a genetic screen, we identified EMI1 as a modulator of PARPi sensitivity in triple-negative breast cancer (TNBC) cells. This function requires the F-box domain of EMI1, through which EMI1 assembles a canonical SCF ubiquitin ligase complex that constitutively targets RAD51 for degradation. In response to genotoxic stress, CHK1-mediated phosphorylation of RAD51 counteracts EMI1-dependent degradation by enhancing RAD51's affinity for BRCA2, leading to RAD51 accumulation. Inhibition of RAD51 degradation restores HRR in BRCA1-depleted cells. Human breast cancer samples display an inverse correlation between EMI1 and RAD51 protein levels. A subset of BRCA1-deficient TNBC cells develop resistance to PARPi by downregulating EMI1 and restoring RAD51-dependent HRR. Notably, reconstitution of EMI1 expression reestablishes PARPi sensitivity both in cellular systems and in an orthotopic mouse model.
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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.