Roles of 17-AAG-induced molecular chaperones and Rma1 E3 ubiquitin ligase in folding and degradation of Pendrin.

[pendred syndrome]

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 Hsp 90 inhibitor , facilitates the folding of Pendrin through heat shock transcription factor 1 (Hsf 1 )-dependent induction of molecular chaperones . Furthermore , we demonstrate that Rma 1 , an E 3 ubiquitin ligase localized in the ER membrane , is involved in Pendrin degradation .