ArticleJournal of molecular medicine (Berlin, Germany)2020
SUMOylation of Pdia3 exacerbates proinsulin misfolding and ER stress in pancreatic beta cells.
Article in Journal of molecular medicine (Berlin, Germany), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- ROS-SUMO Crosstalk in Oxidative Stress: Disease Mechanisms and Reproductive Health.Antioxidants (Basel, Switzerland) · 2026Review
- PDIA3 Inhibition Facilitates Sensitivity of IKE-Induced Ferroptosis via STAT3/LCN2 Axis to Improve Glioblastoma Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Rapid protein carbonylation and decreased insulin secretion induced by inflammatory oxidative stress compounds.Free radical biology & medicine · 2026Article
- PDIA3 rs2788, a risk factor for metabolic syndrome, interacted negatively with antihypertensive medications.Scientific reports · 2025Article
- Dynamic Rendition of Adipose Genes Under Epigenetic Regulation: Revealing New Mechanisms of Obesity Occurrence.Current issues in molecular biology · 2025Review
- PDIA3 orchestrates effector T cell program by serving as a chaperone to facilitate the non-canonical nuclear import of STAT1 and PKM2.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Post-translational modifications: emerging directors of cell-fate decisions during endoplasmic reticulum stress in Arabidopsis thaliana.Biochemical Society transactions · 2024Review
- Tissue adaptation to metabolic stress: insights from SUMOylation.Frontiers in endocrinology · 2024Review
- Enhanced insulin activity achieved in VDRa/b ablation zebrafish.Frontiers in endocrinology · 2023Article
- One-Step Genotyping Method in loxP-Based Conditional Knockout Mice Generated by CRISPR-Cas9 Technology.Molecular biotechnology · 2022Article
- The Pancreatic ß-cell Response to Secretory Demands and Adaption to Stress.Endocrinology · 2021Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SUMOylation has long been recognized to regulate multiple biological processes in pancreatic beta cells, but its impact on proinsulin disulfide maturation and endoplasmic reticulum (ER) stress remains elusive. Herein, we conducted comparative proteomic analyses of SUMOylated proteins in primary mouse/human islets following proinflammatory cytokine stimulation. Cytokine challenge rendered beta cells to undergo a SUMOylation turnover manifested by the changes of SUMOylation substrates and SUMOylation levels for multiple substrates. Our data support that SUMOylation may play a crucial role to regulate proinsulin misfolding and ER stress at least by targeting Protein Disulfide Isomerase a3 (Pdia3). SUMOylation regulates Pdia3 enzymatic activity, subcellular localization, and protein binding ability. Furthermore, SUMOylation of Pdia3 exacerbated proinsulin misfolding and ER stress, and repressed Stat3 activation. In contrast, disruption of Pdia3 SUMOylation markedly rescued the outcomes. Collectively, our study expands the understanding how SUMOylation regulates ER stress in beta cells, which shed light on developing potential strategies against beta cell dysfunction.
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Registered trials
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.