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Related Concept Videos

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...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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...
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...

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Related Experiment Video

Updated: Jul 11, 2026

Measurements of Physiological Stress Responses in C. Elegans
10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

ERADicate ER stress or die trying.

Margaret M Kincaid1, Antony A Cooper

  • 1Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri, USA.

Antioxidants & Redox Signaling
|September 22, 2007
PubMed
Summary

The unfolded protein response (UPR) manages endoplasmic reticulum (ER) stress by regulating protein folding and degradation. Failure of these UPR pathways can lead to cell death and diseases like diabetes.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Endoplasmic reticulum (ER) stress triggers the unfolded protein response (UPR), a protective network involving PERK, ATF6, and IRE1 sensors.
  • The UPR aims to restore ER homeostasis by modulating protein translation, chaperone expression, and ER-associated degradation (ERAD).

Purpose of the Study:

  • To elucidate the multifaceted mechanisms employed by the UPR to mitigate ER stress.
  • To explore novel pathways involved in reducing protein load within the ER.
  • To understand the consequences of UPR pathway failure in disease pathogenesis.

Main Methods:

  • Investigated the roles of ER transmembrane sensors PERK, ATF6, and IRE1 in mediating the UPR.
  • Analyzed the UPR's coordination of protein translation, chaperone upregulation, and ERAD.

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Last Updated: Jul 11, 2026

Measurements of Physiological Stress Responses in C. Elegans
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  • Examined newly identified UPR mechanisms including IRE1-mediated mRNA degradation, preemptive quality control, enhanced forward trafficking, and autophagy.

    • Main Results:

    • The UPR orchestrates protein synthesis downregulation, chaperone upregulation, and ERAD component enhancement to resolve ER stress.
    • Prolonged, futile protein folding attempts during ER stress can generate reactive oxygen species (ROS) and induce cell death.
    • Novel UPR mechanisms include IRE1's role in degrading specific secretory protein mRNAs, preemptive quality control, enhanced protein export, and autophagy.

    Conclusions:

    • The UPR is a critical cellular defense against ER stress, employing diverse strategies to manage protein homeostasis.
    • Failure or saturation of UPR pathways can result in cellular dysfunction and contribute to diseases such as diabetes and neurodegenerative disorders.
    • Understanding these complex UPR pathways offers insights into disease mechanisms and potential therapeutic targets.