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Updated: May 16, 2026
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Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae
Published on: April 18, 2016
The mammalian endoplasmic reticulum-associated degradation system
James A Olzmann1, Ron R Kopito, John C Christianson
1Department of Biology, Stanford University, Stanford, California 94305, USA.
Cold Spring Harbor Perspectives in Biology
|December 13, 2012
Summary
The endoplasmic reticulum (ER) machinery ensures proper protein folding. Misfolded proteins are degraded via ER-associated degradation (ERAD), a conserved process involving ubiquitin-proteasome system targeting.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The endoplasmic reticulum (ER) synthesizes a significant portion of the eukaryotic proteome.
- Proper protein folding and assembly are critical for proteins destined for the secretory pathway.
- ER-associated degradation (ERAD) removes misfolded proteins via the ubiquitin-proteasome system.
Purpose of the Study:
- To elucidate the organization of the core ERAD machinery in mammalian cells.
- To detail the modular structure of ERAD components.
- To highlight the conserved nature of ERAD across eukaryotes.
Main Methods:
- Review of genetic and biochemical studies, particularly from yeast models.
- Analysis of the modular organization of ERAD machinery.
- Focus on the mammalian cell context for ERAD mechanisms.
Main Results:
- ERAD involves substrate selection, ER membrane dislocation, ubiquitination, and proteasomal degradation.
- The ERAD machinery features ER membrane-embedded ubiquitin ligases.
- This system links ER lumenal recognition to cytoplasmic degradation pathways.
Conclusions:
- The core ERAD machinery is highly conserved in eukaryotes.
- Understanding ERAD in mammalian cells builds upon foundational knowledge from yeast.
- The modular organization facilitates efficient degradation of misfolded proteins.
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