ArticleCell death and differentiation2022
Deubiquitinase OTUD6A promotes breast cancer progression by increasing TopBP1 stability and rendering tumor cells resistant to DNA-damaging therapy.
Article in Cell death and differentiation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- OTUD6A promotes de novo pyrimidine synthesis by deubiquitinating and stabilizing CAD in cervical cancer.Oncogene · 2026Article
- Pan-cancer proteogenomic interrogation of the ubiquitin-proteasome system.Cell death and differentiation · 2026Article
- CRISPR/Cas9-mediated knockout of TopBP1 shifts the Bax/Bcl-2 balance toward apoptosis in MCF7 breast cancer cells.Molecular biology reports · 2026Article
- Targeting the OTU family: a core therapeutic strategy for reshaping the immunosuppressive microenvironment and reversing drug resistance in HCC by coordinating the autophagy-ferroptosis balance.Cell death discovery · 2026Review
- OTUD6A in Airway Epithelial Cells Exacerbates Allergic Asthma by Promoting Airway Inflammation and Airway Remodeling Through Deubiquitination of hResistin/mRELMα.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PRDM1 restricts bladder cancer progression and enhances chemosensitivity by suppressing OTUD6A-mediated deubiquitination of CDC6.Cell death & disease · 2026Article
- OTUD6A drives dopaminergic neuronal degeneration of Parkinson's disease through deubiquitinating ACTG1 in neuronal cells.Acta pharmaceutica Sinica. B · 2026Article
- OTU deubiquitinases as immune-circuit editors: from human immunopathology to therapeutic prioritization.Frontiers in immunology · 2026Review
- OTU deubiquitinases in disease: roles and targeting.Trends in molecular medicine · 2026Review
- Multi-omic characterization of consensus molecular subtype 1 (CMS1) colorectal cancer with dampened immune response improves precision medicine.Molecular oncology · 2025Article
- Dynamic Arginine Methylation of YBX1 Relay Controls Its Phase Separation and Chemoradiotherapy Resistance in Rectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- USP5-Rich Apoptotic Extracellular Vesicles Regulate Nucleus Pulposus Cells Apoptosis and DNA Damage Repair by Preventing E2F1 Proteasomal Degradation.Journal of extracellular vesicles · 2025Article
- OTU deubiquitinases in cancer pathogenesis and precision therapy.American journal of cancer research · 2025Review
- Dissecting the dual role of OTU family proteins in tumor progression and immune escape.Frontiers in immunology · 2025Review
- Deubiquitinating Enzyme OTUDs: Focus on Cancers and Antiviral Response.Oncology research · 2025Review
- A comprehensive molecular characterization of a claudin-low luminal B breast tumor.Biology direct · 2024Article
- Selenomethionine suppresses head and neck squamous cell carcinoma progression through TopBP1/ATR and TCAB1 signaling.Histology and histopathology · 2024Article
- E3 ubiquitin ligase UBR5 promotes gemcitabine resistance in pancreatic cancer by inducing O-GlcNAcylation-mediated EMT via destabilization of OGA.Cell death & disease · 2024Article
- Deubiquitination of CDC6 by OTUD6A promotes tumour progression and chemoresistance.Molecular cancer · 2024Article
- SF3A2 promotes progression and cisplatin resistance in triple-negative breast cancer via alternative splicing of MKRN1.Science advances · 2024Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The DNA damage response (DDR) is critical for maintaining cellular homeostasis and genome integrity. Mounting evidence has shown that posttranslational protein modifications play vital roles in the DDR. In this study, we showed that deubiquitinase OTUD6A is involved in the DDR and is important for maintaining genomic stability. Mechanistically, in response to DNA damage, the abundance of OTUD6A was increased; meanwhile, PP2A interacted with OTUD6A and dephosphorylated OTUD6A at sites S70/71/74, which promoted nuclear localization of OTUD6A. Subsequently, OTUD6A was recruited to the damage site, where it interacted with TopBP1 and blocked the interaction between TopBP1 and its ubiquitin E3 ligase UBR5, decreasing K48-linked polyubiquitination and increasing the stability of TopBP1. OTUD6A depletion impaired CHK1 S345 phosphorylation and blocked cell cycle progression under DNA replication stress. Consistently, knockout of OTUD6A rendered mice hypersensitive to irradiation, shortened survival, and inhibited tumor growth by regulating TopBP1 in xenografted nude mice. Moreover, OTUD6A is expressed at high levels in breast cancer, and OTUD6A overexpression promotes cell proliferation, migration and invasion, indicating that dysregulation of OTUD6A expression contributes to genomic instability and is associated with tumor development. In summary, this study demonstrates that OTUD6A plays a critical role in promoting tumor cell resistance to chemoradiotherapy by deubiquitinating and stabilizing TopBP1.
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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.