Title
High ER stress in beta-cells stimulates intracellular degradation of misfolded insulin
GSBS Program
Biochemistry & Molecular Pharmacology
UMMS Affiliation
Graduate School of Biomedical Sciences; Program in Gene Function and Expression; Program in Molecular Medicine
Date
10-7-2004
Document Type
Article
Medical Subject Headings
Animals; COS Cells; Cercopithecus aethiops; Diabetes Mellitus; Disease Models, Animal; Endoplasmic Reticulum; Humans; Insulin; Islets of Langerhans; Mice; Mice, Inbred Strains; Proteasome Endopeptidase Complex; inhibitors; Protein Conformation; *Protein Folding; Protein Subunits; Ubiquitin; Ubiquitin-Protein Ligases
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
Endoplasmic reticulum (ER) stress, which is caused by the accumulation of misfolded proteins in the ER, elicits an adaptive response, the unfolded protein response (UPR). One component of the UPR, the endoplasmic reticulum-associated protein degradation (ERAD) system, has an important function in the survival of ER stressed cells. Here, we show that HRD1, a component of the ERAD system, is upregulated in pancreatic islets of the Akita diabetes mouse model and enhances intracellular degradation of misfolded insulin. High ER stress in beta-cells stimulated mutant insulin degradation through HRD1 to protect beta-cells from ER stress and ensuing death. If HRD1 serves the same function in humans, it may serve as a target for therapeutic intervention in diabetes.
Rights and Permissions
Citation: Biochem Biophys Res Commun. 2004 Nov 5;324(1):166-70. Link to article on publisher's site