ArticleBMC cancer2020
Tumor suppressor OTUD3 induces growth inhibition and apoptosis by directly deubiquitinating and stabilizing p53 in invasive breast carcinoma cells.
Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 39 citations in OpenAlex.
- The E3 ligase β-TRCP1 earmarks OTUD3 for destruction to fine-tune cGAS activation.The Journal of biological chemistry · 2026Article
- BHLHE22, targeted by deubiquitinating enzyme OTUD3, exerts an antitumor role in triple-negative breast cancer progression via transcriptionally inhibiting CDT1.Breast cancer research : BCR · 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
- The dual role of OTUD3 in cancer: mechanisms and therapeutic implications.Cancer cell international · 2025Review
- OTUD4 suppresses colorectal cancer progression through deubiquitinating p53.Discover oncology · 2025Article
- Research progress of DUB enzyme in breast cancer.Clinical and experimental medicine · 2025Review
- Phosphorylation enhanced OTUD3 deubiquitination ARID3A promotes the progress of cholangiocarcinoma.Oncogene · 2025Article
- OTUD3 inhibits breast cancer cell metastasis by regulating TGF-β pathway through deubiquitinating SMAD7.Cancer cell international · 2025Article
- The deubiquitinase OTUD3 plays a neuroprotective role by reducing ferroptosis induced by cerebral ischaemia reperfusion via stabilizing PLK1 via deubiquitination.Clinical and translational medicine · 2025Article
- CCDC154 knockdown inhibits growth of liver cancer via suppressing expression of Snail.European journal of medical research · 2025Article
- Dissecting the dual role of OTU family proteins in tumor progression and immune escape.Frontiers in immunology · 2025Review
- OTUD7B is a new deubiquitinase targeting p53.Theranostics · 2025Article
- Deubiquitinating Enzyme OTUDs: Focus on Cancers and Antiviral Response.Oncology research · 2025Review
- Review
- The deubiquitinase OTUD3 stabilizes IRP2 expression to reduce hippocampal neuron ferroptosis via the p53/PTGS2 pathway to ameliorate cerebral ischemia-reperfusion injury.European journal of medical research · 2024Article
- The role of ubiquitination in health and disease.MedComm · 2024Review
- Research progress in deubiquitinase OTUD3.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Review
- Sm-like 5 knockdown inhibits proliferation and promotes apoptosis of colon cancer cells by upregulating p53, CDKN1A and TNFRSF10B.World journal of gastrointestinal oncology · 2024Article
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundP53 pathway inactivation plays an important role in the process of breast cancer tumorigenesis. Post-translational protein modification abnormalities have been confirmed to be an important mechanism underlying inactivation of p53. Numerous deubiquitinating enzymes are aberrantly expressed in breast cancer, and a few deubiquitination enzymes can deubiquitinate and stabilize p53. Here, we report that ovarian tumor (OTU) deubiquitinase 3 (OTUD3) is a deubiquitylase of p53 in breast carcinoma (BC).
methodsCorrelations between the mRNA expression levels of OTUD3, TP53 and PTEN and the prognosis of BC were assessed with the Kaplan-Meier Plotter tool. OTUD3 protein expression in 80 pairs of specimens in our cohort was examined by immunohistochemistry and western blotting. The relationship among OTUD3, p53, and p21 proteins was analyzed. Half-life analysis and ubiquitylation assay were performed to elucidate the molecular mechanism by which OTUD3 stabilizes p53. The interaction between OTUD3 and p53 in BC cells was verified by a co-immunoprecipitation assay and GST pulldown experiments. MTS assay for proliferation detection, detection of apoptosis induced by cisplatin and colony formation assay were employed to investigate the functional effects of OTUD3 on breast cancer cells.
resultsOTUD3 downregulation is correlated with a poor prognosis in BC patients. OTUD3 expression is decreased in breast cancer tissues and not associated with the histological grade. OTUD3 also inhibits cell proliferation and clone formation and increases the sensitivity of BC cells to apoptosis induced by chemotherapy drugs. Reduced OTUD3 expression accompanied by decreased p53 abundance is correlated with human breast cancer progression. Ectopic expression of wild-type OTUD3, but not its catalytically inactive mutant, stabilizes and activates p53. Mechanistically, OTUD3 interacts directly with p53 through the amino-terminal OTU region. Finally, OTUD3 protects p53 from murine double minute 2 (Mdm2)-mediated ubiquitination and degradation, enabling the deubiquitination of p53 in BC cells.
conclusionsIn summary, we found that OTUD3 may be a potential therapeutic target for restoring p53 function in breast cancer cells and suggest that the OTUD3-p53 signaling axis may play a critical role in tumor suppression.
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