High ER stress in β-cells stimulates intracellular degradation of misfolded insulin
| Autor: | Kathryn L. Lipson, Jenny R. Allen, Fumihiko Urano, Linh X. Nguyen, Anthony Hackett, Karen E. Sargent |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Proteasome Endopeptidase Complex
Protein Folding medicine.medical_specialty Protein Conformation Ubiquitin-Protein Ligases medicine.medical_treatment Biophysics Mice Inbred Strains Protein degradation Endoplasmic-reticulum-associated protein degradation Endoplasmic Reticulum Biochemistry Islets of Langerhans Mice Downregulation and upregulation Internal medicine Chlorocebus aethiops Diabetes Mellitus medicine Animals Humans Insulin Molecular Biology Ubiquitin Chemistry Endoplasmic reticulum Pancreatic islets Cell Biology Cell biology Disease Models Animal Protein Subunits Endocrinology medicine.anatomical_structure COS Cells Unfolded protein response Proteasome Inhibitors Intracellular |
| Zdroj: | Biochemical and Biophysical Research Communications. 324:166-170 |
| ISSN: | 0006-291X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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