Proteasomes and ubiquitin are involved in the turnover of the wild-type prion protein
| Autor: | Lior Horonchik, Anat Yanai, Albert Taraboulos, Salit Tzaban, Yifat Yedidia |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cytoplasm
Proteasome Endopeptidase Complex Leupeptins animal diseases Lactacystin CHO Cells macromolecular substances Endoplasmic-reticulum-associated protein degradation Endoplasmic Reticulum Article General Biochemistry Genetics and Molecular Biology Mice chemistry.chemical_compound Ubiquitin Multienzyme Complexes Cricetinae Tumor Cells Cultured Animals ERAD pathway PrPC Proteins Protease Inhibitors Molecular Biology Brefeldin A General Immunology and Microbiology biology General Neuroscience Wild type Membrane Proteins nervous system diseases Cysteine Endopeptidases Cytosol Solubility chemistry Proteasome Biochemistry biology.protein Protein Processing Post-Translational |
| Zdroj: | The EMBO Journal. 20:5383-5391 |
| ISSN: | 1460-2075 |
| DOI: | 10.1093/emboj/20.19.5383 |
| Popis: | Prion diseases propagate by converting a normal glycoprotein of the host, PrP(C), into a pathogenic "prion" conformation. Several misfolding mutants of PrP(C) are degraded through the ER-associated degradation (ERAD)-proteasome pathway. In their infectious form, prion diseases such as bovine spongiform encephalopathy involve PrP(C) of wild-type sequence. In contrast to mutant PrP, wild-type PrP(C) was hitherto thought to be stable in the ER and thus immune to ERAD. Using proteasome inhibitors, we now show that approximately 10% of nascent PrP(C) molecules are diverted into the ERAD pathway. Cells incubated with N-acetyl-leucinal-leucinal-norleucinal (ALLN), lactacystin or MG132 accumulated both detergent-soluble and insoluble PrP species. The insoluble fraction included an unglycosylated 26 kDa PrP species with a protease-resistant core, and a M(r) "ladder" that contained ubiquitylated PrP. Our results show for the first time that wild-type PrP(C) molecules are subjected to ERAD, in the course of which they are dislocated into the cytosol and ubiquitylated. The presence of wild-type PrP molecules in the cytosol may have potential pathogenic implications. |
| Databáze: | OpenAIRE |
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