title: Roles of 17-AAG-induced molecular chaperones and Rma1 E3 ubiquitin ligase in folding and degradation of Pendrin.
abstract: 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.
authors: School of Chemical and Biological Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-744, Republic of Korea.
authors: Kanghyun
authors: K
authors: Lee
authors: Tae-Joon
authors: TJ
authors: Hong
authors: Ji-Sook
authors: JS
authors: Hahn
mesh_terms: D016227:Benzoquinones / Q000494:pharmacology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D026901:Membrane Transport Proteins / Q000737:chemistry*; D018832:Molecular Chaperones / Q000737:chemistry*; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D000076988:Sulfate Transporters; D014157:Transcription Factors / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry*
chemical_list: D016227:Benzoquinones; C505032:CFTR protein, human; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D047029:Lactams, Macrocyclic; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D014157:Transcription Factors; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C112765:tanespimycin; C111501:RNF5 protein, human; D044767:Ubiquitin-Protein Ligases