ArticleThe Journal of biological chemistry2016
Ubiquitin D Regulates IRE1α/c-Jun N-terminal Kinase (JNK) Protein-dependent Apoptosis in Pancreatic Beta Cells.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- Ubiquitin and ubiquitin-like modifications in the endoplasmic reticulum stress response.The FEBS journal · 2026Review
- Ubiquitin D Correlates with Disease Severity and T Cell Infiltration in Cholestasis: Evidence from Integrated Bioinformatics and Experimental Analyses.International journal of medical sciences · 2026Article
- Ubiquitin-like Proteins in Autoimmune Diseases: Current Evidence and Therapeutic Opportunities.Immune network · 2025Review
- Review
- Pan-cancer landscape of UBD/FAT10 and experimental validation in esophageal carcinoma.Frontiers in oncology · 2025Article
- tRNA-derived fragments in T lymphocyte-beta cell crosstalk and in type 1 diabetes pathogenesis in NOD mice.Diabetologia · 2024Article
- Roles of Neuronal Protein Kinase Cε on Endoplasmic Reticulum Stress and Autophagic Formation in Diabetic Neuropathy.Molecular neurobiology · 2024Article
- β Cell Stress and Endocrine Function During T1D: What Is Next to Discover?Endocrinology · 2023Article
- Ubiquitin D promotes the progression of rheumatoid arthritis via activation of the p38 MAPK pathway.Molecular medicine reports · 2023Article
- IRE1/XBP1 and endoplasmic reticulum signaling - from basic to translational research for cardiovascular disease.Current opinion in physiology · 2022Article
- Methylmercury Induces Mitochondria- and Endoplasmic Reticulum Stress-Dependent Pancreatic β-Cell Apoptosis via an Oxidative Stress-Mediated JNK Signaling Pathway.International journal of molecular sciences · 2022Article
- FAT10 is a Prognostic Biomarker and Correlated With Immune Infiltrates in Skin Cutaneous Melanoma.Frontiers in molecular biosciences · 2022Article
- Review
- The case for FAT10 as a novel target in fatty liver diseases.Frontiers in pharmacology · 2022Review
- The Pancreatic ß-cell Response to Secretory Demands and Adaption to Stress.Endocrinology · 2021Review
- Endoplasmic reticulum stress, cell death and tumor: Association between endoplasmic reticulum stress and the apoptosis pathway in tumors (Review).Oncology reports · 2021Review
- The Roles of FGF21 and ALCAT1 in Aerobic Exercise-Induced Cardioprotection of Postmyocardial Infarction Mice.Oxidative medicine and cellular longevity · 2021Article
- Protein Kinases Signaling in Pancreatic Beta-cells Death and Type 2 Diabetes.Advances in experimental medicine and biology · 2021Article
- Pathological β-Cell Endoplasmic Reticulum Stress in Type 2 Diabetes: Current Evidence.Frontiers in endocrinology · 2021Review
- Inositol Requiring Enzyme (IRE), a multiplayer in sensing endoplasmic reticulum stress.Animal cells and systems · 2021Review
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Authors and funding
12 authors.
Funding
Abstract
Pro-inflammatory cytokines contribute to pancreatic beta cell apoptosis in type 1 diabetes at least in part by inducing endoplasmic reticulum (ER) stress and the consequent unfolded protein response (UPR). It remains to be determined what causes the transition from "physiological" to "apoptotic" UPR, but accumulating evidence indicates that signaling by the ER transmembrane protein IRE1α is critical for this transition. IRE1α activation is regulated by both intra-ER and cytosolic cues. We evaluated the role for the presently discovered cytokine-induced and IRE1α-interacting protein ubiquitin D (UBD) on the regulation of IRE1α and its downstream targets. UBD was identified by use of a MAPPIT (mammalian protein-protein interaction trap)-based IRE1α interactome screen followed by comparison against functional genomic analysis of human and rodent beta cells exposed to pro-inflammatory cytokines. Knockdown of UBD in human and rodent beta cells and detailed signal transduction studies indicated that UBD modulates cytokine-induced UPR/IRE1α activation and apoptosis. UBD expression is induced by the pro-inflammatory cytokines interleukin (IL)-1β and interferon (IFN)-γ in rat and human pancreatic beta cells, and it is also up-regulated in beta cells of inflamed islets from non-obese diabetic mice. UBD interacts with IRE1α in human and rodent beta cells, modulating IRE1α-dependent activation of JNK and cytokine-induced apoptosis. Our data suggest that UBD provides a negative feedback on cytokine-induced activation of the IRE1α/JNK pro-apoptotic pathway in cytokine-exposed beta cells.
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