دورية أكاديمية
The chaperone protein BiP binds to a mutant prion protein and mediates its degradation by the proteasome.
| العنوان: | The chaperone protein BiP binds to a mutant prion protein and mediates its degradation by the proteasome. |
|---|---|
| المؤلفون: | Jin T; Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA., Gu Y, Zanusso G, Sy M, Kumar A, Cohen M, Gambetti P, Singh N |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2000 Dec 08; Vol. 275 (49), pp. 38699-704. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print Cited Medium: Print ISSN: 0021-9258 (Print) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Protein Folding*, Carrier Proteins/*metabolism , Molecular Chaperones/*metabolism , Prions/*chemistry , Prions/*metabolism, Amino Acid Substitution ; Animals ; Carrier Proteins/chemistry ; Cricetinae ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum Chaperone BiP ; Glycosylation ; Heat-Shock Proteins/chemistry ; Heat-Shock Proteins/metabolism ; Humans ; Kinetics ; Molecular Chaperones/chemistry ; Neuroblastoma ; Prions/genetics ; Recombinant Proteins/chemistry ; Recombinant Proteins/metabolism ; Transfection ; Tumor Cells, Cultured |
| مستخلص: | Familial prion diseases are thought to result from a change in structure of the mutant prion protein (PrP), which takes a pathogenic conformation. We have examined the role of molecular chaperones in the folding of normal and mutant PrP Q217R (PrP(217)) in transfected neuroblastoma cells. In a previous report we showed that, although most of the PrP(217) forms escape the endoplasmic reticulum quality control system and aggregate in post-Golgi compartments, a significant proportion of PrP(217) retains the C-terminal glycosylphosphatidyl inositol signal peptide (PrP32), and does not exit the endoplasmic reticulum (Singh, N., Zanusso, G., Chen, S. G., Fujioka, H., Richardson, S., Gambetti, P., and Petersen, R. B. (1997) J. Biol. Chem. 272, 28461-28470). We have now studied the folding and turnover of PrP32 to understand the mechanism by which abnormal PrP forms cause cellular toxicity in our cell culture model and in the human brain carrying the Gerstmann-Sträussler-Scheinker disease Q217R mutation. In this report, we show that PrP32 remains associated with the chaperone BiP for an abnormally prolonged period of time and is degraded by the proteasomal pathway. This study is the first demonstration that BiP is chaperoning the folding of PrP and plays a role in maintaining the quality control in the PrP maturation pathway. Our data provide new insight into the diverse pathways of mutant PrP metabolism and neurotoxicity. |
| المشرفين على المادة: | 0 (Carrier Proteins) 0 (Endoplasmic Reticulum Chaperone BiP) 0 (Heat-Shock Proteins) 0 (Molecular Chaperones) 0 (Prions) 0 (Recombinant Proteins) |
| تواريخ الأحداث: | Date Created: 20000906 Date Completed: 20010118 Latest Revision: 20211203 |
| رمز التحديث: | 20240627 |
| DOI: | 10.1074/jbc.M005543200 |
| PMID: | 10970892 |
| قاعدة البيانات: | MEDLINE |
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