Stimulation of ERAD of misfolded null Hong Kong α1-antitrypsin by golgi α1,2-mannosidases
Stimulation of ERAD of misfolded null Hong Kong α1-antitrypsin by golgi α1,2-mannosidases
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DOI：
10.1016/j.bbrc.2007.08.057
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发表时间：
2007-10-26
影响因子：
3.1
通讯作者：
Herscovics, Annette
中科院分区：
文献类型：
--
作者：
Hosokawa, Nobuko;You, Zhipeng;Herscovics, Annette
末端错误折叠或未组装的蛋白质在称为ERAD（内质网相关蛋白质降解）的过程中被细胞质泛素-蛋白酶体途径降解。ER α 1，2-甘露糖苷酶I和EDEM的过表达靶向ERAD的错误折叠糖蛋白，最可能是由于N-聚糖的修剪。在这里，我们证明了高尔基体α 1，2-甘露糖苷酶IA，IB和IC的过表达也加速了末端错误折叠的人α 1-抗胰蛋白酶变体null（香港）（NHK）的ERAD，以及293细胞中NHK上N-聚糖的甘露糖修剪。虽然转染的NHK主要定位在ER中，但一些NHK也与高尔基体标记物共定位，这表明通过高尔基体α 1，2-甘露糖苷酶进行的甘露糖修剪也可有助于NHK降解。(c)2007爱思唯尔公司All rights reserved.
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 alpha 1,2-mannosidase I and EDEMs target misfolded glycoproteins for ERAD, most likely due to trimming of N-glycans. Here we demonstrate that overexpression of Golgi alpha 1,2-mannosidase IA, IB, and IC also accelerates ERAD of terminally misfolded human alpha 1-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 alpha 1,2-mannosidases can also contribute to NHK degradation. (c) 2007 Elsevier Inc. All rights reserved.