[HTML][HTML] Ubiquitin ligase gp78 targets unglycosylated prion protein PrP for ubiquitylation and degradation
Prion protein PrP is a central player in several devastating neurodegenerative disorders,
including mad cow disease and Creutzfeltd-Jacob disease. Conformational alteration of PrP
into an aggregation-prone infectious form PrPSc can trigger pathogenic events. How levels
of PrP are regulated is poorly understood. Human PrP is known to be degraded by the
proteasome, but the specific proteolytic pathway responsible for PrP destruction remains
elusive. Here, we demonstrate that the ubiquitin ligase gp78, known for its role in protein …
including mad cow disease and Creutzfeltd-Jacob disease. Conformational alteration of PrP
into an aggregation-prone infectious form PrPSc can trigger pathogenic events. How levels
of PrP are regulated is poorly understood. Human PrP is known to be degraded by the
proteasome, but the specific proteolytic pathway responsible for PrP destruction remains
elusive. Here, we demonstrate that the ubiquitin ligase gp78, known for its role in protein …
Prion protein PrP is a central player in several devastating neurodegenerative disorders, including mad cow disease and Creutzfeltd-Jacob disease. Conformational alteration of PrP into an aggregation-prone infectious form PrPSc can trigger pathogenic events. How levels of PrP are regulated is poorly understood. Human PrP is known to be degraded by the proteasome, but the specific proteolytic pathway responsible for PrP destruction remains elusive. Here, we demonstrate that the ubiquitin ligase gp78, known for its role in protein quality control, is critical for unglycosylated PrP ubiquitylation and degradation. Furthermore, C-terminal sequences of PrP protein are crucial for its ubiquitylation and degradation. Our study reveals the first ubiquitin ligase specifically involved in prion protein PrP degradation and PrP sequences crucial for its turnover. Our data may lead to a new avenue to control PrP level and pathogenesis.
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