GSBS Student Publications

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

Related Resources

Link to article in PubMed

Journal Title

Biochemical and biophysical research communications

PubMed ID

15464997