ArticleCancer cell international2019
The deubiquitinating enzyme OTUD1 antagonizes BH3-mimetic inhibitor induced cell death through regulating the stability of the MCL1 protein.
Article in Cancer cell international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Balancing Ubiquitination and Deubiquitination in Apoptotic Protein Stability and Cancer Cell Survival.International journal of molecular sciences · 2026Review
- Deubiquitinating enzymes in cervical cancer: Molecular mechanisms and therapeutic implications (Review).International journal of oncology · 2026Review
- Hypoxia promotes progression of cervical cancer by modulating the ATXN3-enhanced P53 stability or STAT5 phosphorylation.Cell death discovery · 2026Article
- The deubiquitinase OTUD1 orchestrates cisplatin chemosensitivity of non-small cell lung cancer through destabilizing RAD23B/XPC.Oncogene · 2025Article
- Evaluation of Metabolic Characteristics Induced by Deoxynivalenol in 3D4/21 Cells.Animals : an open access journal from MDPI · 2025Article
- USP37 as a novel regulator of NRF2 protein stability and chemoresistance in HCC.Discover oncology · 2025Article
- Review
- The Deubiquitinase OTUD1 Influences HIV-1 Release by Regulating the Host Restriction Factor BST-2.Viruses · 2025Article
- Deubiquitinating Enzyme OTUDs: Focus on Cancers and Antiviral Response.Oncology research · 2025Review
- Review
- Deubiquitinases in cancer.Nature reviews. Cancer · 2023Review
- Pleiotropic Roles of a KEAP1-Associated Deubiquitinase, OTUD1.Antioxidants (Basel, Switzerland) · 2023Review
- The deubiquitinase OTUD1 inhibits non-small cell lung cancer progression by deubiquitinating and stabilizing KLF4.Thoracic cancer · 2022Article
- OTUD1 stabilizes PTEN to inhibit the PI3K/AKT and TNF-alpha/NF-kappaB signaling pathways and sensitize ccRCC to TKIs.International journal of biological sciences · 2022Article
- The regulation of neuronal autophagy and cell survival by MCL1 in Alzheimer's disease.Acta materia medica · 2022Article
- Inhibition of BMI-1 Induces Apoptosis through Downregulation of DUB3-Mediated Mcl-1 Stabilization.International journal of molecular sciences · 2021Article
- ZIPK activates the IL-6/STAT3 signaling pathway and promotes cisplatin resistance in gastric cancer cells.FEBS open bio · 2021Article
- Article
- Knockdown of otubain 2 inhibits liver cancer cell growth by suppressing NF-κB signaling.The Kaohsiung journal of medical sciences · 2020Article
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMyeloid cell leukaemia 1 (MCL1) is a pro-survival Bcl-2 family protein that plays important roles in cell survival, proliferation, differentiation and tumourigenesis. MCL1 is a fast-turnover protein that is degraded via an ubiquitination/proteasome-dependent mechanism. Although several E3 ligases have been discovered to promote the ubiquitination of MCL1, the deubiquitinating enzyme (DUB) that regulates its stability requires further investigation.
methodsThe immunoprecipitation was used to determine the interaction between OTUD1 and MCL1. The ubiquitination assays was performed to determine the regulation of MCL1 by OTUD1. The cell viability was used to determine the regulation of BH3-mimetic inhibitor induced cell death by OTUD1. The survival analysis was used to determine the relationship between OTUD1 expression levels and the survival rate of cancer patients.
resultsBy screening a DUB expression library, we determined that the deubiquitinating enzyme OTUD1 regulates MCL1 protein stability in an enzymatic-activity dependent manner. OTUD1 interacts with MCL1 and promotes its deubiquitination. Knockdown of OTUD1 increases the sensitivity of tumour cells to the BH3-mimetic inhibitor ABT-263, while overexpression of OTUD1 increases tumour cell tolerance of ABT-263. Furthermore, bioinformatics analysis data reveal that OTUD1 is a negative prognostic factor for liver cancer, ovarian cancer and specific subtypes of breast and cervical cancer.
conclusionsThe deubiquitinating enzyme OTUD1 antagonizes BH3-mimetic inhibitor induced cell death through regulating the stability of the MCL1 protein. Thus, OTUD1 could be considered as a therapeutic target for curing these cancers.
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