ArticleDiabetologia2013
Otubain 2 is a novel promoter of beta cell survival as revealed by siRNA high-throughput screens of human pancreatic islets.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 42 citations in OpenAlex.
- Article
- Immunopeptidome mining reveals a novel ERS-induced target in T1D.Cellular & molecular immunology · 2024Article
- Harnessing Human Pluripotent Stem Cell-Derived Pancreatic In Vitro Models for High-Throughput Toxicity Testing and Diabetes Drug Discovery.Handbook of experimental pharmacology · 2023Article
- Deubiquitinase OTUB2 exacerbates the progression of colorectal cancer by promoting PKM2 activity and glycolysis.Oncogene · 2022Article
- The Emerging Role of OTUB2 in Diseases: From Cell Signaling Pathway to Physiological Function.Frontiers in cell and developmental biology · 2022Review
- Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors.Cancers · 2021Review
- WIDOCK: a reactive docking protocol for virtual screening of covalent inhibitors.Journal of computer-aided molecular design · 2021Article
- Rapid Covalent-Probe Discovery by Electrophile-Fragment Screening.Journal of the American Chemical Society · 2019Article
- miR-29a-3p inhibits growth, proliferation, and invasion of papillary thyroid carcinoma by suppressing NF-κB signaling via direct targeting of OTUB2.Cancer management and research · 2019Article
- OTUB2 stabilizes U2AF2 to promote the Warburg effect and tumorigenesis via the AKT/mTOR signaling pathway in non-small cell lung cancer.Theranostics · 2019Article
- Identification of Biologically Active Pyrimido[5,4-b]indoles That Prolong NF-κB Activation without Intrinsic Activity.ACS combinatorial science · 2017Article
- TM7SF3, a novel p53-regulated homeostatic factor, attenuates cellular stress and the subsequent induction of the unfolded protein response.Cell death and differentiation · 2017Article
- High-throughput Functional Genomics Identifies Regulators of Primary Human Beta Cell Proliferation.The Journal of biological chemistry · 2016Article
- High-throughput screening of small interfering ribonucleic acid identifies important modulators in islet dysfunction and apoptosis.Journal of diabetes investigation · 2015Article
- The human otubain2-ubiquitin structure provides insights into the cleavage specificity of poly-ubiquitin-linkages.PloS one · 2015Article
- OTUB2 Promotes Homologous Recombination Repair Through Stimulating Rad51 Expression in Endometrial Cancer.Cell transplantationArticle
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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
aims/hypothesisPro-inflammatory cytokines induce death of beta cells and hamper engraftment of transplanted islet mass. Our aim was to reveal novel genes involved in this process, as a platform for innovative therapeutic approaches.
methodsSmall interfering RNA (siRNA) high-throughput screening (HTS) of primary human islets was employed to identify novel genes involved in cytokine-induced beta cell apoptosis. Dispersed human islets from nine human donors, treated with a combination of TNF-α, IL-1β and IFN-γ were transfected with ∼730 different siRNAs. Caspase-3/7 activity was measured, results were analysed and potential anti- and pro-apoptotic genes were identified.
resultsDispersed human pancreatic islets appeared to be suitable targets for performance of siRNA HTS. Using this methodology we found a number of potential pro- and anti-apoptotic target hits that have not been previously associated with pancreatic beta cell death. One such hit was the de-ubiquitinating enzyme otubain 2 (OTUB2). OTUB2 knockdown increased caspase-3/7 activity in MIN6 cells and primary human islets and inhibited insulin secretion and increased nuclear factor-κB (NF-κB) activity both under basal conditions and following cytokine treatment.
conclusionsUse of dispersed human islets provides a new platform for functional HTS in a highly physiological system. Employing this technique enabled the identification of OTUB2 as a novel promoter of viability and insulin secretion in human beta cells. OTUB2 acts through the inhibition of NF-κB signalling, which is deleterious to beta cell survival. siRNA screens of human islets may therefore identify new targets, such as OTUB2, for therapeutic intervention in type 1 diabetes and islet transplantation.
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