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...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2014-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3979651?pdf=render |
id |
doaj-b9528e2ebfb5419eaa60cf8cb8259d08 |
---|---|
record_format |
Article |
spelling |
doaj-b9528e2ebfb5419eaa60cf8cb8259d082020-11-25T01:42:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9229010.1371/journal.pone.0092290Ubiquitin ligase gp78 targets unglycosylated prion protein PrP for ubiquitylation and degradation.Jia ShaoVitnary ChoeHaili ChengYien Che TsaiAllan M WeissmanShiwen LuoHai RaoPrion 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.http://europepmc.org/articles/PMC3979651?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jia Shao Vitnary Choe Haili Cheng Yien Che Tsai Allan M Weissman Shiwen Luo Hai Rao |
spellingShingle |
Jia Shao Vitnary Choe Haili Cheng Yien Che Tsai Allan M Weissman Shiwen Luo Hai Rao Ubiquitin ligase gp78 targets unglycosylated prion protein PrP for ubiquitylation and degradation. PLoS ONE |
author_facet |
Jia Shao Vitnary Choe Haili Cheng Yien Che Tsai Allan M Weissman Shiwen Luo Hai Rao |
author_sort |
Jia Shao |
title |
Ubiquitin ligase gp78 targets unglycosylated prion protein PrP for ubiquitylation and degradation. |
title_short |
Ubiquitin ligase gp78 targets unglycosylated prion protein PrP for ubiquitylation and degradation. |
title_full |
Ubiquitin ligase gp78 targets unglycosylated prion protein PrP for ubiquitylation and degradation. |
title_fullStr |
Ubiquitin ligase gp78 targets unglycosylated prion protein PrP for ubiquitylation and degradation. |
title_full_unstemmed |
Ubiquitin ligase gp78 targets unglycosylated prion protein PrP for ubiquitylation and degradation. |
title_sort |
ubiquitin ligase gp78 targets unglycosylated prion protein prp for ubiquitylation and degradation. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3979651?pdf=render |
work_keys_str_mv |
AT jiashao ubiquitinligasegp78targetsunglycosylatedprionproteinprpforubiquitylationanddegradation AT vitnarychoe ubiquitinligasegp78targetsunglycosylatedprionproteinprpforubiquitylationanddegradation AT hailicheng ubiquitinligasegp78targetsunglycosylatedprionproteinprpforubiquitylationanddegradation AT yienchetsai ubiquitinligasegp78targetsunglycosylatedprionproteinprpforubiquitylationanddegradation AT allanmweissman ubiquitinligasegp78targetsunglycosylatedprionproteinprpforubiquitylationanddegradation AT shiwenluo ubiquitinligasegp78targetsunglycosylatedprionproteinprpforubiquitylationanddegradation AT hairao ubiquitinligasegp78targetsunglycosylatedprionproteinprpforubiquitylationanddegradation |
_version_ |
1725034296072208384 |