High ER stress in beta-cells stimulates intracellular degradation of misfolded insulin
AuthorsAllen, Jenny R.
Nguyen, Linh X.
Sargent, Karen E.G.
Lipson, Kathryn L.
UMass Chan AffiliationsProgram in Molecular Medicine
Program in Gene Function and Expression
Graduate School of Biomedical Sciences
Document TypeJournal Article
KeywordsAnimals; 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
Medicine and Health Sciences
MetadataShow full item record
AbstractEndoplasmic 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.
SourceBiochem Biophys Res Commun. 2004 Nov 5;324(1):166-70. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/33779
Related ResourcesLink to article in PubMed