An HRD/DER-independent ER quality control mechanism involves Rsp5p-dependent ubiquitination and ER-Golgi transport.
J Cell Biol
; 158(1): 91-101, 2002 Jul 08.
Article
em En
| MEDLINE
| ID: mdl-12105183
ABSTRACT
We have identified a new pathway of ER-associated degradation in Saccharomyces cerevisiae that functions separately from the HRD/DER pathway comprised of Hrd1p, Hrd3p, Der1p, and Ubc7p. This pathway, termed Hrd1p independent-proteolysis (HIP), is capable of recognizing and degrading both lumenal (CPY* and PrA*), and integral membrane proteins (Sec61-2p) that misfold in the ER. CPY* overexpression likely saturates the HRD/DER pathway and activates the HIP pathway, so the slowed degradation kinetics of CPY* in a hrd1 Delta strain is restored to a wild-type rate when CPY* is overexpressed. Substrates of HIP require vesicular trafficking between the ER and Golgi apparatus before degradation by the ubiquitin-proteasome system. Ubiquitination of HIP substrates does not involve the HRD/DER pathway ubiquitin ligase Hrd1p, but instead uses another ubiquitin ligase, Rsp5p. HIP is regulated by the unfolded protein response as Ire1p is necessary for the degradation of CPY* when overexpressed, but not when CPY* is expressed at normal levels. Both the HIP and HRD/DER pathways contribute to the degradation of CPY*, and only by eliminating both is CPY* degradation completely blocked.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
/
Proteínas Fúngicas
/
Glicoproteínas de Membrana
/
Proteínas de Saccharomyces cerevisiae
/
Ubiquitina
/
Complexos Ubiquitina-Proteína Ligase
/
Enzimas de Conjugação de Ubiquitina
/
Ubiquitina-Proteína Ligases
/
Retículo Endoplasmático
/
Complexo de Golgi
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Estados Unidos