Degradation of a Mutant Secretory Protein, α1-Antitrypsin Z, in the Endoplasmic Reticulum Requires Proteasome Activity

• DOI: 10.1074/jbc.271.37.22791
• Publication Date: 2002-07-26T14:57:46Z
• Authors: Dongfeng Qu; Jeffrey H. Teckman; Satoshi Omura; David H. Perlmutter
• Keywords: Calnexin; Lactacystin; Endoplasmic-reticulum-associated protein degradation; Protein Degradation; Chaperone (clinical); Secretory protein; Proteolysis

Degradation of proteins that are retained in the quality control apparatus endoplasmic reticulum (ER) has been attributed to a third proteolytic system, distinct from lysosomal and cytoplasmic ubiquitin-dependent proteosomal pathways. However, several recent studies have shown ER degradation mutant membrane protein, CFTRΔF508, is at least part mediated side by 26 S proteasome. In this study, we examined possibility secretory protein α1-antitrypsin (α1-AT) Z, associated with infantile liver disease adult-onset emphysema α1-AT deficiency, The results show specific proteasome inhibitor, lactacystin, inhibits α1-ATZ transfected human fibroblast cell lines cell-free microsomal translocation system. Although it relatively easy conceptualize how transmembrane like CFTRΔF508 might be accessible on aspect for ubiquitination proteasome, more difficult occur luminal polypeptide. that, once within lumen ER, interacts molecular chaperone calnexin specifically induces polyubiquitination calnexin. results, therefore, provide evidence its localization, molecule first attacking tail molecules α1-ATZ.