Thumbnail
Access Restriction
Open

Author Gnann, Andreas ♦ Riordan, John R. ♦ Wolf, Dieter H.
Source CiteSeerX
Content type Text
File Format PDF
Language English
Subject Domain (in DDC) Computer science, information & general works ♦ Data processing & computer science
Subject Keyword Common Mutation ♦ Different Mutation ♦ Used Yeast Mutant ♦ Der3p Hrd1p ♦ Human Cftr Quality Control ♦ White Population ♦ Yeast Relative ♦ Mammalian Orthologue Edem ♦ Degradation Process ♦ Yeast Cell ♦ Yeast Saccharomyces Cerevisiae ♦ Degradation Mechanism ♦ Cftr Degradation ♦ Htm1 Deficiency ♦ Lectin Htm1p ♦ Widespread Hereditary Disease ♦ Quality Control ♦ Component Share Homology ♦ Protein Quality Control ♦ Degradation System ♦ New Therapeutic Approach ♦ Cystic Fibrosis ♦ Endoplasmic Reticulum-associated Degradation ♦ Mammalian Counterpart ♦ Ubiquitin Protein ♦ Erad System ♦ New Component ♦ Complete Degradation
Description 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, �F508, 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.
Educational Role Student ♦ Teacher
Age Range above 22 year
Educational Use Research
Education Level UG and PG ♦ Career/Technical Study
Learning Resource Type Article
Publisher Institution the lectins Htm1p/EDEM and the Cdc48 protein complex in yeast. Mol Biol Cell 2004