Encyclopedia of Cancer

Living Edition
| Editors: Manfred Schwab

Endoplasmic Reticulum Stress

  • Alex van Vliet
  • Patrizia Agostinis
Living reference work entry
DOI: https://doi.org/10.1007/978-3-642-27841-9_1888-2



The endoplasmic reticulum (ER) is an organelle with several essential functions in eukaryotic cells. The ER is both a major intracellular calcium store and the place where proteins are synthesized, folded, modified, and delivered to their final cell surface or extracellular destination. Moreover, in mammalian cells, the ER is the site of sterols and lipids synthesis. Disturbance in any of these functions, which results in the disruption of the proper folding and secretory capacity of the ER and increased load of unfolded proteins in its lumen, defines a condition known as “ER stress.” ER stress activates a complex and multifaceted intracellular signal transduction pathway that is essentially designed to re-establish ER homeostasis. Inability to restore ER functions induces cell death, which is usually in the form of apoptosis. ER stress contributes to the etiology of several human pathologies, including diabetes,...


Endoplasmic Reticulum Endoplasmic Reticulum Stress Endoplasmic Reticulum Function Endoplasmic Reticulum Homeostasis Translational Block 
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Ca2+-release channels

Membrane receptors localized in the sarcoplasmic/endoplasmic reticulum that once activated mediates the release of Ca2+ from the ER to the cytosol.


A Ca2+ binding integral protein of the ER that interacts and assists the folding of proteins that carry monoglucosylated N-linked glycans.

Conformational diseases

A group of heterologous disorders, which include Alzheimer’s, Parkinson’s and Creutzfeldt-Jakob diseases, which arise from the dysfunctional aggregation of proteins in non-native conformations.

Damage associated molecular patterns

Subset of endogenous molecules that have physiological roles within living cells and which acquire immunomodulatory functions when exposed to the extracellular milieu during the cell death process. Once surface exposed or released, DAMPs are sensed by the innate immune system and act as activators of antigen-presenting cells (APCs) to stimulate adaptive immunity.

ER quality-control

The molecular apparatus that monitors the maturation and transport of proteins in the ER and targets nonnative conformers for degradation.

ER-associated protein degradation

The mechanism whereby unfolded or misfolded proteins are re-exported from the ER lumen into the cytosol to undergo proteasomal degradation.

Eukaryotic initiation factor-2 α

A subunit of eIF2 that recruits Met-tRNAi to the mRNA-40S ribosome complex in its active GTP-binding form. Stress induced eIF2α phosphorylation by a family of protein kinases including PERK, PKR, GCN2, and HRI, prevents the assembly of the eIF2-initiation complex, thereby inhibiting global translation.


Conjugates reduced glutathione to toxic electrophile that have arisen through oxidative stress, for example.

Immunogenic cell death

A cell death modality that, in contrast to the physiological caspase mediated-tolerogenic apoptosis, stimulates immunogenicity of the cancer cell along with a protective anticancer immune response in vivo.


Proteins that bind carbohydrates.

Molecular chaperones

A family of cellular proteins that mediate the correct assembly and disassembly of nascent polypeptides, by the reversible interaction with nascent polypeptide chains.

Native conformation (protein)

The most energetically favorable state adopted by a protein, which usually corresponds to the conformation with the lowest free energy.

Nuclear factor (erythroid-derived 2)-like 2

Transcription factor that can induce the expression of anti-oxidant proteins.


A 26S multiprotein complex that catalyses the degradation of polyubiquitylated proteins.

Protein disulphide isomerase (PDI)

An enzyme belonging to the thiol-disulphide oxidoreductases family of proteins that catalyzes the oxidation, isomerization, and reduction of disulphide bonds.

Reactive Oxygen Species

A group of chemically reactive molecules and free radical molecules deriving from the incomplete reduction of molecular oxygen. Examples of which are superoxide and peroxide.

Regulated Ire1-dependent decay

Activated IRE1 is able to utilize its endoribonuclease domain in the degradation of mRNA which harbor a specific XBP-1-like consensus site.

Secretory pathway

A complex network of eukaryotic cell organelles that is central to and mediates the folding, maturation, and trafficking of secreted and transmembrane proteins.


A pump situated in the membrane of the sarcoplasmic/endoplasmic reticulum that couples ATP hydrolysis to the import of Ca2+ from the cytosol to the ER lumen.

Type I transmembrane protein

A transmembrane protein that exposes its carboxyl terminus into the cytosol.

Type II transmembrane protein

A transmembrane protein that exposes its amino terminus into the cytosol.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of Cellular and Molecular Medicine, Cell Death Research and Therapy LabKU Leuven Campus GasthuisbergLeuvenBelgium