ArticleNature communications2017
Ubiquitin-specific protease 21 stabilizes BRCA2 to control DNA repair and tumor growth.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 57 citations in OpenAlex.
- Inhibition of the U12-type splicing factor ZCRB1 mediates retention of the USP21 minor intron to suppress malignant progression in hepatocellular carcinoma.Hepatology international · 2026Article
- Regulatory roles of five key USP family deubiquitinases in cancer: from mechanisms to targeted therapy advances.Frontiers in pharmacology · 2026Review
- Mechanism of USP21 autoinhibition and histone H2AK119 deubiquitination.Science advances · 2025Article
- Ubiquitin-Specific Protease Inhibitors for Cancer Therapy: Recent Advances and Future Prospects.Biomolecules · 2025Review
- Roles of deubiquitinases in urologic cancers (Review).Oncology letters · 2024Review
- USP15 regulates radiation-induced DNA damage and intestinal injury through K48-linked deubiquitination and stabilisation of ATM.Molecular medicine (Cambridge, Mass.) · 2024Article
- USP21-mediated G3BP1 stabilization accelerates proliferation and metastasis of esophageal squamous cell carcinoma via activating Wnt/β-Catenin signaling.Oncogenesis · 2024Article
- DoUBLing up: ubiquitin and ubiquitin-like proteases in genome stability.The Biochemical journal · 2024Review
- USP30 promotes the progression of breast cancer by stabilising Snail.Cancer gene therapy · 2024Article
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Discovery and Characterization of BAY-805, a Potent and Selective Inhibitor of Ubiquitin-Specific Protease USP21.Journal of medicinal chemistry · 2023Article
- Dipeptidyl peptidase 9 triggers BRCA2 degradation and promotes DNA damage repair.EMBO reports · 2022Article
- USP21 regulates Hippo signaling to promote radioresistance by deubiquitinating FOXM1 in cervical cancer.Human cell · 2022Article
- Genome-wide association, RNA-seq and iTRAQ analyses identify candidate genes controlling radicle length of wheat.Frontiers in plant science · 2022Article
- A necroptosis -related signature for predicting prognosis and immunotherapy in hepatocellular carcinoma.Frontiers in genetics · 2022Article
- Insights Into the Properties, Biological Functions, and Regulation of USP21.Frontiers in pharmacology · 2022Review
- Alterations of Chromatin Regulators in the Pathogenesis of Urinary Bladder Urothelial Carcinoma.Cancers · 2021Review
- JUMPt: Comprehensive Protein Turnover Modeling of In Vivo Pulse SILAC Data by Ordinary Differential Equations.Analytical chemistry · 2021Article
- Identification of prognostic long intergenic non-coding RNAs as competing endogenous RNAs with KRAS mutations in colorectal cancer.Oncology letters · 2021Article
- Guardians of the Genome: BRCA2 and Its Partners.Genes · 2021Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Tumor growth relies on efficient DNA repair to mitigate the detrimental impact of DNA damage associated with excessive cell division. Modulating repair factor function, thus, provides a promising strategy to manipulate malignant growth. Here, we identify the ubiquitin-specific protease USP21 as a positive regulator of BRCA2, a key mediator of DNA repair by homologous recombination. USP21 interacts with, deubiquitinates and stabilizes BRCA2 to promote efficient RAD51 loading at DNA double-strand breaks. As a result, depletion of USP21 decreases homologous recombination efficiency, causes an increase in DNA damage load and impairs tumor cell survival. Importantly, BRCA2 overexpression partially restores the USP21-associated survival defect. Moreover, we show that USP21 is overexpressed in hepatocellular carcinoma, where it promotes BRCA2 stability and inversely correlates with patient survival. Together, our findings identify deubiquitination as a means to regulate BRCA2 function and point to USP21 as a potential therapeutic target in BRCA2-proficient tumors.BRCA2 is essential for the repair of DNA damage; therefore, defects in BRCA2 are associated with tumorigenesis but also with increased susceptibility to genotoxic stress. Here the authors show that USP21 regulates the ability of tumor cells to repair damaged DNA by regulating BRCA2 stability.
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Registered trials
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