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Roles of 17‐AAG‐induced molecular chaperones and Rma1 E3 ubiquitin ligase in folding and degradation of Pendrin
Author(s) -
Lee Kanghyun,
Hong Tae-Joon,
Hahn Ji-Sook
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.06.023
Subject(s) - pendrin , ubiquitin ligase , chemistry , ubiquitin , endoplasmic reticulum , microbiology and biotechnology , hsf1 , transmembrane protein , hsp90 , protein degradation , heat shock protein , biochemistry , hsp70 , biology , receptor , gene , transporter
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.