Roles of 17-AAG-induced molecular chaperones and Rma1 E3 ubiquitin ligase in folding and degradation of Pendrin
Roles of 17-AAG-induced molecular chaperones and Rma1 E3 ubiquitin ligase in folding and degradation of Pendrin
复制标题
DOI：
10.1016/j.febslet.2012.06.023
复制
发表时间：
2012-07-30
期刊：
影响因子：
3.5
通讯作者：
Hahn, Ji-Sook
中科院分区：
文献类型：
--
作者：
Lee, Kanghyun;Hong, Tae-Joon;Hahn, Ji-Sook
垂丝蛋白是一种跨膜氯/阴离子交换器，在甲状腺、肾脏和内耳中高度表达。内质网(ER)-不正确折叠的垂垂蛋白突变体的滞留被认为是Pendred综合征的主要原因。然而，人们对悬垂蛋白的折叠和降解机制知之甚少。在这里，我们报告了Hsp90抑制剂17-AAG的处理，通过热休克转录因子1(HSF1)依赖的分子伴侣诱导，促进了支链蛋白的折叠。此外，我们还证明了Rma1，一种定位于内质网膜上的E3泛素连接酶，参与了膜脂的降解。(C)2012年欧洲生化学会联合会。爱思唯尔出版，版权所有。
Pendrin is a transmembrane chloride/anion exchanger highly expressed in thyroid, kidney, and inner ear. Endoplasmic reticulum (ER)-retention of improperly folded Pendrin mutants is considered as the major cause for Pendred syndrome. However, the folding and degradation mechanisms of Pendrin are poorly understood. Here, we report that treatment of 17-AAG, an Hsp90 inhibitor, facilitates the folding of Pendrin through heat shock transcription factor 1 (Hsf1)-dependent induction of molecular chaperones. Furthermore, we demonstrate that Rma1, an E3 ubiquitin ligase localized in the ER membrane, is involved in Pendrin degradation. (c) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.