ArticleCell reports2018
ZRANB1 Is an EZH2 Deubiquitinase and a Potential Therapeutic Target in Breast Cancer.
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Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38citing papers in PubMed
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38 citing papers in PubMed, 58 citations in OpenAlex.
- ZRANB1 depletion inhibits neuroblastoma progression by destabilizing MYCN through EZH2-mediated deubiquitination.Cell biology and toxicology · 2026Article
- Research progress of DUB enzyme in breast cancer.Clinical and experimental medicine · 2025Review
- LAMP5 modulates IRF4 stability and nuclear transport: a critical mechanism in myeloma progression and therapy.Oncogene · 2025Article
- USP8-Governed MDA5 Homeostasis Promotes Innate Immunity and Autoimmunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Tumour microbiota activities associated with local recurrence in ER + PR + breast cancer.Cancer biomarkers : section A of Disease markers · 2025Article
- Deubiquitinase OTUD6A alleviates acetaminophen-induced liver injury by targeting EZH2 to reduce cell death in hepatocytes.Acta pharmaceutica Sinica. B · 2025Article
- Mitochondrial PTRH2 controls the deubiquitinase TRABID to regulate mt-ND5 stability and metabolism.PNAS nexus · 2025Article
- OTU deubiquitinases in cancer pathogenesis and precision therapy.American journal of cancer research · 2025Review
- Exploring vaginal microbiome: from traditional methods to metagenomic next-generation sequencing-a systematic review.Frontiers in microbiology · 2025Review
- Dissecting the dual role of OTU family proteins in tumor progression and immune escape.Frontiers in immunology · 2025Review
- Review
- The role of deubiquitinase USP2 in driving bladder cancer progression by stabilizing EZH2 to epigenetically silence SOX1 expression.Translational oncology · 2024Article
- USP26 as a hepatitis B virus-induced deubiquitinase primes hepatocellular carcinogenesis by epigenetic remodeling.Nature communications · 2024Article
- OTUD7B knockdown inhibits the proliferation and stemness of breast cancer cells by destabilizing FOXM1.Oncology letters · 2024Article
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- The deubiquitinase ZRANB1 is an E3 ubiquitin ligase for SLC7A11 and regulates ferroptotic resistance.The Journal of cell biology · 2023Article
- USP53 Exerts Tumor-Promoting Effects in Triple-Negative Breast Cancer by Deubiquitinating CRKL.Cancers · 2023Article
- DUBing Primary Tumors of the Central Nervous System: Regulatory Roles of Deubiquitinases.Biomolecules · 2023Review
- ZRANB1 is an NBS1 deubiquitinase and a potential target to overcome radioresistance and PARP inhibitor resistance in triple-negative breast cancer.Genes & diseases · 2023Article
- TRABID inhibition activates cGAS/STING-mediated anti-tumor immunity through mitosis and autophagy dysregulation.Nature communications · 2023Article
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Authors and funding
36 authors at 7 institutions in 3 countries.
Peijing ZhangDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China. Electronic address: zhangpeijing@hust.edu.cn.
Zhenna XiaoDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Science, Houston, TX 77030, USA.
Shouyu WangDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Mutian ZhangCenter for Epigenetics & Disease Prevention, Texas A&M University Institute of Biosciences & Technology, Houston, TX 77030, USA.
Yongkun WeiDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Qinglei HangDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jongchan KimDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Fan YaoDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cristian Rodriguez-AguayoDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Baochau N TonDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Minjung LeeCenter for Epigenetics & Disease Prevention, Texas A&M University Institute of Biosciences & Technology, Houston, TX 77030, USA; Department of Molecular & Cellular Medicine, College of Medicine, Texas A&M University, College Station, TX 77843, USA.
Yumeng WangGraduate Program in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, TX 77030, USA; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Zhicheng ZhouDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Liyong ZengDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Xiaoyu HuDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Sarah E LawhonDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ashley N SiverlyDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Xiaohua SuDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jia LiCenter for Epigenetics & Disease Prevention, Texas A&M University Institute of Biosciences & Technology, Houston, TX 77030, USA.
Xiaoping XieDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Xuhong ChengDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Liang-Chiu LiuDivision of Breast Surgery, Department of Surgery, China Medical University Hospital, Taichung 404, Taiwan.
Hui-Wen ChangDepartment of Pathology, China Medical University Hospital, Taichung 404, Taiwan.
Shu-Fen ChiangCancer Center, China Medical University Hospital, Taichung 404, Taiwan.
Gabriel Lopez-BeresteinDepartment of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Anil K SoodDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Junjie ChenDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
M James YouDepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Shao-Cong SunDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Han LiangGraduate Program in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, TX 77030, USA; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yun HuangCenter for Epigenetics & Disease Prevention, Texas A&M University Institute of Biosciences & Technology, Houston, TX 77030, USA; Department of Molecular & Cellular Medicine, College of Medicine, Texas A&M University, College Station, TX 77843, USA.
Xianbin YangAM Biotechnologies, Houston, TX 77034, USA.
Deqiang SunCenter for Epigenetics & Disease Prevention, Texas A&M University Institute of Biosciences & Technology, Houston, TX 77030, USA.
Yutong SunDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Mien-Chie HungDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University, Taichung 404, Taiwan.
Li MaDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Science, Houston, TX 77030, USA. Electronic address: lma4@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USChina Medical University · TWPrevention Institute · USBaylor College of Medicine · USRaptamer Discovery Group (United States) · USTexas A&M University · USThe University of Texas Health Science Center at Houston · US
Funding
Regulation of metastasis and epithelial-mesenchymal transition by microRNAsR01CA166051 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MA, LI · 2012 to 2023
$3.4MGenetic Epidemiology of non-Hodgkin LymphomaR01CA200703 · NCI · MAYO CLINIC ROCHESTER · PI CERHAN, JAMES R · 2016 to 2020
$3.3MEpithelial-mesenchymal transition regulators in radioresistance and DNA repairR01CA181029 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MA, LI · 2014 to 2018
$1.7MCHARACTERIZATION AND TARGETED THERAPY OF T-ALL DEFICIENT FOR PTEN AND INK4A/ARFR01CA164346 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI YOU, M. JAMES · 2012 to 2015
$1.2MNew Reagents for RNA-based Therapeutic TechnologiesR44GM086937 · NIGMS · AM BIOTECHNOLOGIES, LLC · PI YANG, XIANBIN · 2013 to 2014
$997kNew Building Blocks for the Synthesis of Modified RNAsR43GM100777 · NIGMS · AM BIOTECHNOLOGIES, LLC · PI LI, NA, YANG, XIANBIN · 2012 to 2012
$180kNew Reagents for the Synthesis of Phosphorodithioate-Modified 2'-O-Methyl RNAsR43GM086937 · NIGMS · AM BIOTECHNOLOGIES, LLC · PI DURLAND, ROSS HOWARD, YANG, XIANBIN · 2011 to 2011
$157kNCI NIH HHS R01 CA164346NCI NIH HHS R01 CA166051NCI NIH HHS R01 CA181029NCI NIH HHS R01 CA200703NIGMS NIH HHS R43 GM086937NIGMS NIH HHS R43 GM100777NIGMS NIH HHS R44 GM086937
Abstract
Although EZH2 enzymatic inhibitors have shown antitumor effects in EZH2-mutated lymphoma and ARID1A-mutated ovarian cancer, many cancers do not respond because EZH2 can promote cancer independently of its histone methyltransferase activity. Here we identify ZRANB1 as the EZH2 deubiquitinase. ZRANB1 binds, deubiquitinates, and stabilizes EZH2. Depletion of ZRANB1 in breast cancer cells results in EZH2 destabilization and growth inhibition. Systemic delivery of ZRANB1 small interfering RNA (siRNA) leads to marked antitumor and antimetastatic effects in preclinical models of triple-negative breast cancer (TNBC). Intriguingly, a small-molecule inhibitor of ZRANB1 destabilizes EZH2 and inhibits the viability of TNBC cells. In patients with breast cancer, ZRANB1 levels correlate with EZH2 levels and poor survival. These findings suggest the therapeutic potential for targeting the EZH2 deubiquitinase ZRANB1.
Indexed as
AnimalsCell Line, TumorEnhancer of Zeste Homolog 2 ProteinFemaleHEK293 CellsHumansKaplan-Meier EstimateMiceMice, Inbred C57BLProtein BindingRNA InterferenceRNA, Small InterferingTransplantation, HeterologousTriple Negative Breast NeoplasmsUbiquitin-Specific ProteasesZinc FingersEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanRNA, Small InterferingUbiquitin-Specific Proteasesbreast cancerdeubiquitinaseEZH2ZRANB1
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