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Export of Misfolded Proteins out of the ER

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...

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Related Experiment Video

Updated: Jun 24, 2026

Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae

Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae

Published on: April 18, 2016

Adapter-mediated substrate selection for endoplasmic reticulum-associated degradation.

Kathleen Corcoran¹, Xiaoli Wang, Lonnie Lybarger

¹Department of Immunobiology, University of Arizona, Tucson, AZ 85724, USA.

The Journal of Biological Chemistry

|April 16, 2009

Summary

Endoplasmic reticulum-associated degradation (ERAD) utilizes adapter proteins to recruit diverse substrates for ubiquitination. This mechanism ensures specificity for ERAD E3 ligases, like mK3, independent of substrate sequence.

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Last Updated: Jun 24, 2026

Cycloheximide Chase Analysis of Protein Degradation in Saccharomyces cerevisiae

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Published on: April 18, 2016

Growth-based Determination and Biochemical Confirmation of Genetic Requirements for Protein Degradation in Saccharomyces cerevisiae

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Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Published on: May 10, 2022

Area of Science:

Cell Biology
Molecular Biology
Immunology

Background:

Endoplasmic reticulum-associated degradation (ERAD) involves ubiquitin ligases (E3) targeting diverse substrates.
Specificity in ERAD is crucial, as E3 ligases must handle varied substrates without relying solely on sequence.
Mechanisms ensuring E3 ligase specificity for multiple, unrelated substrates are not fully understood.

Purpose of the Study:

To investigate the mechanism of substrate selection for the viral ERAD E3 ligase, mK3.
To provide direct evidence for adapter-mediated substrate recruitment in ERAD.
To explore how E3 ligases achieve specificity for structurally diverse substrates.

Main Methods:

Utilized a viral ERAD E3 ligase (mK3) system.
Investigated the role of ER membrane protein complexes in substrate selection.
Assessed ubiquitination of heterologous substrates recruited by ER accessory molecules.

Main Results:

Demonstrated that ER membrane protein complexes are essential for mK3 substrate selection.
Showed that mK3 can ubiquitinate heterologous substrates when recruited by ER accessory proteins.
Identified adapter-mediated recruitment as a key specificity mechanism for mK3.

Conclusions:

Adapter proteins play a critical role in recruiting substrates to ERAD E3 ligases.
This adapter-mediated mechanism explains how E3 ligases can target multiple, sequence-unrelated substrates.
The findings offer insights into both viral and cellular ERAD pathways.