Signaling the Unfolded Protein Response from the Endoplasmic Reticulum*

By Kezhong Zhang, R. Kaufman. Journal of Biological Chemistry, 2004

613 citations recorded by the source corpus.

Eukaryotic cells have a membranous labyrinth network called the endoplasmic reticulum (ER) that extends through the cytoplasm of the cell and is contiguous with the nuclear envelope. Proteins must be correctly folded and assembled in the ER prior to transit to intracellular organelles and the cell surface. As a processing plant for protein folding and posttranslational modification, the ER is exquisitely sensitive to alterations in homeostasis. A number of cellular stress conditions, such as perturbation in calcium homeostasis or redox status, elevated secretory protein synthesis, expression of misfolded proteins, sugar/glucose deprivation, altered glycosylation, and overloading of cholesterol can interfere with oxidative protein folding and subsequently lead to accumulation of unfolded or misfolded proteins in the ER lumen, which constitutes a fundamental threat to the cells. The ER has evolved highly specific signaling pathways to alter transcriptional and translational programs to cope with the accumulation of unfolded or misfolded proteins in the ER lumen. This adaptive response, which couples the ER protein folding load with the ER protein folding capacity, is termed the unfolded protein response (UPR) (1–4). Over the past 10 years, significant progress has been made in understanding the mechanisms and roles of UPR signaling. Here we discuss the basic components of the UPR pathways, the physiological roles of the UPR signaling, and the future direction of the field.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/47acb97766e712f103f8918ee322d125b4e68d67

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1. Guido Kroemer
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1. Guido Kroemer
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Citations in the corpus

• Chronic palmitate but not oleate exposure induces endoplasmic reticulum stress, which may contribute to INS-1 pancreatic beta-cell apoptosis. (2006, background): “D, Immunogold labeling with antibodies to the ER chaperone protein Grp78/BiP shows gold particles lining the edge of the clefts (arrowheads).”
• Cardiotoxicity of the cancer therapeutic agent imatinib mesylate (2006, background): “Because of the pronounced accumulation of membranous debris within, and dilation of, the sarcoplasmic and endoplasmic reticulum in the hearts of imatinib-treated humans and mice, we tested whether the ER stress response pathwa”
• Adipose tissue as an endocrine organ. (2010, background): “In certain pathological stress conditions, such as a high-fat diet, elevated levels of free fatty acids and cytokines have been recognized to lead to the accumulation of improperly folded proteins in the ER lumen and to the activation of the unfolded protein response (UPR) pathway (Zhang and Kaufman”
• Calreticulin exposure dictates the immunogenicity of cancer cell death (2007, background): “5b ), a protein that is typically hyperphosphorylated in ER stress due to the activation of stress kinase”