ArticleThe Journal of biological chemistry2014
Monoubiquitination is critical for ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (Otub1) to suppress UbcH5 enzyme and stabilize p53 protein.
Article in The Journal of biological chemistry, 2014. 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, 52 citations in OpenAlex.
- Otubain deubiquitinases: Multi-layered regulators of cell fate, development, and stress responses across kingdoms.iScience · 2026Review
- UBE2O-mediated ubiquitylation directs cytoplasmic CTNNA1 to promote cell-to-ECM adhesions.EMBO reports · 2025Article
- Eupalinolide B inhibits periodontitis development by targeting ubiquitin conjugating enzyme UBE2D3.MedComm · 2025Article
- OTUB1 Promotes Glioblastoma Growth by Inhibiting the JAK2/STAT1 Signaling Pathway.Journal of Cancer · 2024Article
- Cellular Validation of a Chemically Improved Inhibitor Identifies Monoubiquitination on OTUB2.ACS chemical biology · 2023Article
- miR-221/222 induce instability of p53 By downregulating deubiquitinase YOD1 in acute myeloid leukemia.Cell death discovery · 2023Article
- OTUB1-mediated inhibition of ubiquitination: a growing list of effectors, multiplex mechanisms, and versatile functions.Frontiers in molecular biosciences · 2023Review
- Targeting E2 ubiquitin-conjugating enzyme UbcH5c by small molecule inhibitor suppresses pancreatic cancer growth and metastasis.Molecular cancer · 2022Article
- The ubiquitin hydrolase OTUB1 promotes glioma cell stemness via suppressing ferroptosis through stabilizing SLC7A11 protein.Bioengineered · 2021Article
- Deubiquitinating enzyme OTUB1 promotes cancer cell immunosuppression via preventing ER-associated degradation of immune checkpoint protein PD-L1.Cell death and differentiation · 2021Article
- Regulating tumor suppressor genes: post-translational modifications.Signal transduction and targeted therapy · 2020Review
- OTUB1 Recruits Tumor Infiltrating Lymphocytes and Is a Prognostic Marker in Digestive Cancers.Frontiers in molecular biosciences · 2020Article
- IL-15 in autoimmunity and cancer: O-tu-b or not O-tu-b?Nature immunology · 2019Article
- TGF-β signaling pathway mediated by deubiquitinating enzymes.Cellular and molecular life sciences : CMLS · 2019Review
- Otubain 1: a non-canonical deubiquitinase with an emerging role in cancer.Endocrine-related cancer · 2019Review
- OTUB1 non-catalytically stabilizes the E2 ubiquitin-conjugating enzyme UBE2E1 by preventing its autoubiquitination.The Journal of biological chemistry · 2018Article
- H19 Induces Abdominal Aortic Aneurysm Development and Progression.Circulation · 2018Article
- OTUB1 promotes esophageal squamous cell carcinoma metastasis through modulating Snail stability.Oncogene · 2018Article
- Salmonella enterica Serovar Typhimurium Alters the Extracellular Proteome of Macrophages and Leads to the Production of Proinflammatory Exosomes.Infection and immunity · 2018Article
- TRIM25 Is Required for the Antiviral Activity of Zinc Finger Antiviral Protein.Journal of virology · 2017Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Ovarian tumor domain-containing ubiquitin (Ub) aldehyde binding protein 1 (Otub1) regulates p53 stability and activity via non-canonical inhibition of the MDM2 cognate Ub-conjugating enzyme (E2) UbcH5. However, it is not clear how this activity of Otub1 is regulated in cells. Here we report that Otub1 is monoubiquitinated by UbcH5 in cells and in vitro, primarily at the lysine 59 and 109 residues. This monoubiquitination, in turn, contributes to the activity of Otub1 to suppress UbcH5. The lysine-free Otub1 mutant (Otub1(K0)) fails to be monoubiquitinated and is unable to suppress the Ub-conjugating activity of UbcH5 in vitro and the MDM2-mediated p53 ubiquitination in cells. Consistently, this mutant is unable to stabilize p53, induce apoptosis, and suppress cell proliferation. Overexpression of Otub1(K0) inhibits DNA-damage induced apoptosis. Adding either Lys-59 or Lys-109 back to the Otub1(K0) mutant restores the monoubiquitination of Otub1 and its function to stabilize and activate p53. We further show that UbcH5 preferentially binds to the monoubiquitinated Otub1 via Ub interaction with its backside donor Ub-interacting surface, suggesting that this binding interferes with the self-assembly of Ub-charged UbcH5 (UbcH5∼Ub) conjugates, which is critical for Ub transfer. Thus, our data reveal novel insights into the Otub1 inhibition of E2 wherein monoubiquitination promotes the interaction of Otub1 with UbcH5 and the function to suppress it.
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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.