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Related Concept Videos

Homologous Recombination02:31

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
ER Retrieval Pathway01:45

ER Retrieval Pathway

In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
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The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
Export of Misfolded Proteins out of the ER01:32

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...
Hazard Ratio01:12

Hazard Ratio

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For example, in a clinical trial evaluating a...

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Related Experiment Video

Updated: May 11, 2026

Growth-based Determination and Biochemical Confirmation of Genetic Requirements for Protein Degradation in Saccharomyces cerevisiae
10:57

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

Published on: February 16, 2015

Have you HRD? Understanding ERAD is DOAble!

Nurzian Ismail1, Davis T W Ng

  • 1Temasek Life Sciences Laboratory and Department of Biological Sciences, National University of Singapore, Singapore 117604.

Cell
|July 29, 2006
PubMed
Summary

Two protein complexes at the endoplasmic reticulum membrane recognize and degrade specific misfolded proteins. This discovery clarifies substrate specificity in protein quality control, a key cellular process.

Area of Science:

  • Cellular biology
  • Protein degradation
  • Endoplasmic reticulum function

Background:

  • Misfolded proteins pose a threat to cellular health.
  • Mechanisms for specific protein degradation are not fully understood.
  • The endoplasmic reticulum is a key site for protein folding and quality control.

Purpose of the Study:

  • To elucidate the mechanisms of substrate specificity in protein degradation.
  • To identify the protein factors responsible for recognizing and degrading misfolded proteins.
  • To understand the role of the endoplasmic reticulum membrane in protein quality control.

Main Methods:

  • Investigated protein complexes located at the endoplasmic reticulum membrane.
  • Utilized biochemical and genetic approaches to identify protein substrates.

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Last Updated: May 11, 2026

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  • Analyzed the recognition and degradation pathways of specific protein subsets.
  • Main Results:

    • Identified two distinct protein complexes at the endoplasmic reticulum membrane.
    • Demonstrated that these complexes are responsible for recognizing specific subsets of misfolded proteins.
    • Provided evidence for distinct degradation pathways mediated by these complexes.

    Conclusions:

    • Two distinct protein complexes mediate substrate specificity in protein degradation at the endoplasmic reticulum.
    • These complexes ensure the targeted removal of specific misfolded proteins, maintaining cellular homeostasis.
    • The findings offer new insights into the intricate protein quality control machinery within the cell.