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

Jia Shao, Vitnary Choe, Haili Cheng, Yien Che Tsai, Allan M. Weissman, Shiwen Luo, Hai Rao

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Article numbere92290
JournalPloS one
Volume9
Issue number4
DOIs
StatePublished - Apr 8 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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