Intramembrane protease RHBDL4 cleaves oligosaccharyltransferase subunits to target them for ER-associated degradation.
J Cell Sci
; 133(6)2020 03 26.
Article
em En
| MEDLINE
| ID: mdl-32005703
The endoplasmic reticulum (ER)-resident intramembrane rhomboid protease RHBDL4 generates metastable protein fragments and together with the ER-associated degradation (ERAD) machinery provides a clearance mechanism for aberrant and surplus proteins. However, the endogenous substrate spectrum and with that the role of RHBDL4 in physiological ERAD is mainly unknown. Here, we use a substrate trapping approach in combination with quantitative proteomics to identify physiological RHBDL4 substrates. This revealed oligosaccharyltransferase (OST) complex subunits such as the catalytic active subunit STT3A as substrates for the RHBDL4-dependent ERAD pathway. RHBDL4-catalysed cleavage inactivates OST subunits by triggering dislocation into the cytoplasm and subsequent proteasomal degradation. RHBDL4 thereby controls the abundance and activity of OST, suggesting a novel link between the ERAD machinery and glycosylation tuning.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Degradação Associada com o Retículo Endoplasmático
/
Hexosiltransferases
/
Proteínas de Membrana
Tipo de estudo:
Risk_factors_studies
Idioma:
En
Revista:
J Cell Sci
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Alemanha