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PLoS One. 2014 Apr 8;9(4):e92290. doi: 10.1371/journal.pone.0092290. eCollection 2014.

Ubiquitin ligase gp78 targets unglycosylated prion protein PrP for ubiquitylation and degradation.

Author information

1
The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, China.
2
Department of Molecular Medicine, the University of Texas Health Science Center, San Antonio, Texas, United States of America.
3
Laboratory of Protein Dynamics and Signaling, National Cancer Institute, Frederick, Maryland, United States of America.

Abstract

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.

PMID:
24714645
PMCID:
PMC3979651
DOI:
10.1371/journal.pone.0092290
[Indexed for MEDLINE]
Free PMC Article
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