Abstract
Membrane and secretory proteins fold in the endoplasmic reticulum (ER), and misfolded proteins may be retained and targeted for ER-associated protein degradation (ERAD). To elucidate the mechanism by which an integral membrane protein in the ER is degraded, we studied the fate of the cystic fibrosis transmembrane conductance regulator (CFTR) in the yeast Saccharomyces cerevisiae. Our data indicate that CFTR resides in the ER and is stabilized in strains defective for proteasome activity or deleted for the ubiquitin-conjugating enzymes Ubc6p and Ubc7p, thus demonstrating that CFTR is a bona fide ERAD substrate in yeast. We also found that heat shock protein 70 (Hsp70), although not required for the degradation of soluble lumenal ERAD substrates, is required to facilitate CFTR turnover. Conversely, calnexin and binding protein (BiP), which are required for the proteolysis of ER lumenal proteins in both yeast and mammals, are dispensable for the degradation of CFTR, suggesting unique mechanisms for the disposal of at least some soluble and integral membrane ERAD substrates in yeast.
Bibliography
Zhang, Y., Nijbroek, G., Sullivan, M. L., McCracken, A. A., Watkins, S. C., Michaelis, S., & Brodsky, J. L. (2001). Hsp70 Molecular Chaperone Facilitates Endoplasmic Reticulum-associated Protein Degradation of Cystic Fibrosis Transmembrane Conductance Regulator in Yeast. Molecular Biology of the Cell, 12(5), 1303â1314.
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Dates
Type | When |
---|---|
Created | 12 years, 1 month ago (July 2, 2013, 8:13 p.m.) |
Deposited | 3 years, 5 months ago (Feb. 26, 2022, 9:45 p.m.) |
Indexed | 3 months, 1 week ago (May 16, 2025, 6:05 a.m.) |
Issued | 24 years, 3 months ago (May 1, 2001) |
Published | 24 years, 3 months ago (May 1, 2001) |
Published Print | 24 years, 3 months ago (May 1, 2001) |
@article{Zhang_2001, title={Hsp70 Molecular Chaperone Facilitates Endoplasmic Reticulum-associated Protein Degradation of Cystic Fibrosis Transmembrane Conductance Regulator in Yeast}, volume={12}, ISSN={1939-4586}, url={http://dx.doi.org/10.1091/mbc.12.5.1303}, DOI={10.1091/mbc.12.5.1303}, number={5}, journal={Molecular Biology of the Cell}, publisher={American Society for Cell Biology (ASCB)}, author={Zhang, Yimao and Nijbroek, Gaby and Sullivan, Mara L. and McCracken, Ardythe A. and Watkins, Simon C. and Michaelis, Susan and Brodsky, Jeffrey L.}, editor={Silver, Pamela A.}, year={2001}, month=may, pages={1303–1314} }