Stimulation of ERAD of misfolded null Hong Kong alpha1-antitrypsin by Golgi alpha1,2-mannosidases |
| |
Authors: | Hosokawa Nobuko You Zhipeng Tremblay Linda O Nagata Kazuhiro Herscovics Annette |
| |
Institution: | Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8397, Saitama 332-0012, Japan. |
| |
Abstract: | Terminally misfolded or unassembled proteins are degraded by the cytoplasmic ubiquitin-proteasome pathway in a process known as ERAD (endoplasmic reticulum-associated protein degradation). Overexpression of ER alpha1,2-mannosidase I and EDEMs target misfolded glycoproteins for ERAD, most likely due to trimming of N-glycans. Here we demonstrate that overexpression of Golgi alpha1,2-mannosidase IA, IB, and IC also accelerates ERAD of terminally misfolded human alpha1-antitrypsin variant null (Hong Kong) (NHK), and mannose trimming from the N-glycans on NHK in 293 cells. Although transfected NHK is primarily localized in the ER, some NHK also co-localizes with Golgi markers, suggesting that mannose trimming by Golgi alpha1,2-mannosidases can also contribute to NHK degradation. |
| |
Keywords: | ERAD ER-associated protein degradation NHK α1-antitrypsin null (Hong Kong) α1-AT α1-antitrypsin Golgi IA Golgi α1 2-mannosidase IA ER ManI ER α1 2-mannosidase I Man5 Man5GlcNAc2 Man9 Man9GlcNAc2 Man8 Man8GlcNAc2 G1M9 Glc1Man9GlcNAc2 EndoH endoglycosidase H |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|