Herp enhances ER-associated protein degradation by recruiting ubiquilins.
Biochem Biophys Res Commun
; 369(2): 741-6, 2008 May 02.
Article
em En
| MEDLINE
| ID: mdl-18307982
ABSTRACT
ER-associated protein degradation (ERAD) is a protein quality control system of ER, which eliminates misfolded proteins by proteasome-dependent degradation and ensures export of only properly folded proteins from ER. Herp, an ER membrane protein upregulated by ER stress, is implicated in regulation of ERAD. In the present study, we show that Herp interacts with members of the ubiquilin family, which function as a shuttle factor to deliver ubiquitinated substrates to the proteasome for degradation. Knockdown of ubiquilin expression by small interfering RNA stabilized the ERAD substrate CD3delta, whereas it did not alter or increased degradation of non-ERAD substrates tested. CD3delta was stabilized by overexpressed Herp mutants which were capable of binding to ubiquilins but were impaired in ER membrane targeting by deletion of the transmembrane domain. Our data suggest that Herp binding to ubiquilin proteins plays an important role in the ERAD pathway and that ubiquilins are specifically involved in degradation of only a subset of ubiquitinated targets, including Herp-dependent ERAD substrates.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Proteínas de Transporte
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Proteínas de Ciclo Celular
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Complexo de Endopeptidases do Proteassoma
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Retículo Endoplasmático
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Ubiquitinação
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Proteínas de Membrana
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2008
Tipo de documento:
Article