Proteasomes and ubiquitin are involved in the turnover of the wild-type prion protein

摘要: Prion diseases propagate by converting a normal glycoprotein of the host, PrPC, into pathogenic ‘prion’ conformation. Several misfolding mutants PrPC are degraded through ER-associated degradation (ERAD)–proteasome pathway. In their infectious form, prion such as bovine spongiform encephalopathy involve wild-type sequence. contrast to mutant PrP, was hitherto thought be stable in ER and thus immune ERAD. Using proteasome inhibitors, we now show that ∼10% nascent molecules diverted ERAD Cells incubated with N-acetyl-leucinal-leucinal-norleucinal (ALLN), lactacystin or MG132 accumulated both detergent-soluble insoluble PrP species. The fraction included an unglycosylated 26 kDa species protease-resistant core, Mr ‘ladder’ contained ubiquitylated PrP. Our results for first time subjected ERAD, course which they dislocated cytosol ubiquitylated. presence may have potential implications.