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Reporter-based Growth Assay for Systematic Analysis of Protein Degradation
Published on: November 6, 2014
Novel ubiquitin-dependent quality control in the endoplasmic reticulum
M Feldman1, F Gisou van der Goot
1Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Station 15, CH 1015 Lausanne, Switzerland.
Trends in Cell Biology
|July 28, 2009
Summary
A new mechanism for membrane protein folding in the endoplasmic reticulum (ER) involves ubiquitylation. This process uses mono-ubiquitylation for folding and poly-ubiquitylation for degradation, highlighting the role of de-ubiquitylating enzymes.
Area of Science:
- Cell Biology
- Molecular Biology
- Protein Folding
Background:
- Proteins within the endomembrane system require assisted folding in the endoplasmic reticulum (ER).
- Misfolded proteins are targeted for ER-associated degradation (ERAD).
Purpose of the Study:
- To investigate a novel mechanism promoting the folding of membrane proteins on the cytosolic side of the ER.
- To explore the dual role of ubiquitylation in protein folding and degradation within the ER.
Main Methods:
- Studied the biogenesis of a type-I membrane protein (LRP6 mutant).
- Investigated chaperone binding through mono- and poly-ubiquitylation cycles.
Main Results:
- Proposed a novel folding mechanism involving cycles of mono-ubiquitylation and de-ubiquitylation for chaperone binding.
- Demonstrated that poly-ubiquitylation ultimately leads to ER-associated degradation (ERAD).
Conclusions:
- Ubiquitylation plays a dual role in the ER: promoting folding via mono-ubiquitylation and degradation via poly-ubiquitylation.
- De-ubiquitylating enzymes are potentially crucial for regulating these ER protein processing pathways.
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