Cystic Fibrosis Transmembrane Conductance Regulator Degradation Depends on the Lectins Htm1p/EDEM and the Cdc48 Protein Complex in Yeast
10.1091/mbc.e04-01-0024
Crossref journal-article
American Society for Cell Biology (ASCB)
Molecular Biology of the Cell (1076)
Abstract

Cystic fibrosis is the most widespread hereditary disease among the white population caused by different mutations of the apical membrane ATP-binding cassette transporter cystic fibrosis transmembrane conductance regulator (CFTR). Its most common mutation, ΔF508, leads to nearly complete degradation via endoplasmic reticulum-associated degradation (ERAD). Elucidation of the quality control and degradation mechanisms might give rise to new therapeutic approaches to cure this disease. In the yeast Saccharomyces cerevisiae, a variety of components of the protein quality control and degradation system have been identified. Nearly all of these components share homology with mammalian counterparts. We therefore used yeast mutants defective in the ERAD system to identify new components that are involved in human CFTR quality control and degradation. We show the role of the lectin Htm1p in the degradation process of CFTR. Complementation of the HTM1 deficiency in yeast cells by the mammalian orthologue EDEM underlines the necessity of this lectin for CFTR degradation and highlights the similarity of quality control and ERAD in yeast and mammals. Furthermore, degradation of CFTR requires the ubiquitin protein ligases Der3p/Hrd1p and Doa10p as well as the cytosolic trimeric Cdc48p-Ufd1p-Npl4p complex. These proteins also were found to be necessary for ERAD of a mutated yeast “relative” of CFTR, Pdr5*p.

Bibliography

Gnann, A., Riordan, J. R., & Wolf, D. H. (2004). Cystic Fibrosis Transmembrane Conductance Regulator Degradation Depends on the Lectins Htm1p/EDEM and the Cdc48 Protein Complex in Yeast. Molecular Biology of the Cell, 15(9), 4125–4135.

Authors 3
  1. Andreas Gnann (first)
  2. John R. Riordan (additional)
  3. Dieter H. Wolf (additional)
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Dates
Type When
Created 21 years, 2 months ago (June 23, 2004, 8:19 p.m.)
Deposited 4 years, 2 months ago (June 23, 2021, 2:40 p.m.)
Indexed 1 year, 1 month ago (July 22, 2024, 1:14 a.m.)
Issued 21 years ago (Sept. 1, 2004)
Published 21 years ago (Sept. 1, 2004)
Published Print 21 years ago (Sept. 1, 2004)
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@article{Gnann_2004, title={Cystic Fibrosis Transmembrane Conductance Regulator Degradation Depends on the Lectins Htm1p/EDEM and the Cdc48 Protein Complex in Yeast}, volume={15}, ISSN={1939-4586}, url={http://dx.doi.org/10.1091/mbc.e04-01-0024}, DOI={10.1091/mbc.e04-01-0024}, number={9}, journal={Molecular Biology of the Cell}, publisher={American Society for Cell Biology (ASCB)}, author={Gnann, Andreas and Riordan, John R. and Wolf, Dieter H.}, year={2004}, month=sep, pages={4125–4135} }