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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...
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...
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...
Protein Folding Quality Check in the RER01:29

Protein Folding Quality Check in the RER

ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...

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Related Experiment Video

Updated: Jul 5, 2026

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication
10:12

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication

Published on: June 14, 2024

Untangling the unfolded protein response.

Emma L Davenport1, Gareth J Morgan, Faith E Davies

  • 1Section of Haemato-Oncology, The Institute of Cancer Research, Sutton, Surrey, UK.

Cell Cycle (Georgetown, Tex.)
|April 17, 2008
PubMed
Summary
This summary is machine-generated.

Targeting heat shock proteins (HSP) and the unfolded protein response (UPR) simultaneously offers a novel cancer therapy strategy. This dual approach effectively kills cancer cells by disrupting essential survival pathways.

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Measurements of Physiological Stress Responses in C. Elegans
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Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

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Last Updated: Jul 5, 2026

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication
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Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication

Published on: June 14, 2024

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

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Cancer cells rely on protein families like heat shock proteins (HSP) and the unfolded protein response (UPR) for survival under stress.
  • HSP90 stabilizes critical cancer survival factors such as AKT, ERB2, and HIF1alpha.
  • The UPR is crucial for protein folding and cellular adaptation to the hypoxic tumor microenvironment.

Purpose of the Study:

  • To investigate the potential of targeting HSP90 and UPR pathways simultaneously as a cancer treatment strategy.
  • To highlight the importance of targeting multiple signaling pathways for effective cancer cell killing, using multiple myeloma as a model.

Main Methods:

  • The study focuses on the roles of HSP90 and UPR in cancer cell survival.
  • It explores the implications of inhibiting HSP90 and UPR pathways.
  • The research is based on experimental work in multiple myeloma.

Main Results:

  • Inhibiting HSP90 destabilizes key cancer survival factors and can induce cell death by disrupting the UPR.
  • Targeting HSP90 presents a promising therapeutic strategy due to its role in stabilizing multiple cancer cell survival proteins.
  • Simultaneous targeting of HSP90 and UPR pathways demonstrates potential for effective cancer cell elimination.

Conclusions:

  • Targeting HSP90 inhibitors is a promising therapeutic avenue for a wide range of tumors.
  • Developing specific UPR inhibitors could also be of significant therapeutic interest.
  • Simultaneous targeting of multiple signaling pathways, exemplified by HSP and UPR, is crucial for effectively killing cancer cells.