Unfolded Protein Response

The unfolded protein response (UPR) recognizes and reacts to misfolded protein accumulation in the endoplasmic reticulum (ER). Protein glycosylation enzymes and glycoprotein-binding chaperones in the ER control translocated polypeptide folding. This process keeps proteins in the ER until they are correctly folded before allowing them to proceed to their final destination. Occasionally, cellular stress causes misfolded proteins to accumulate and overwhelm the normal ER protein folding machinery, activating the UPR. Chaperones bound to unfolded proteins in the ER initiate protein kinase cascades that inhibit translation, reverse translocation, activate ER-specific ubiquitination enzymes, and even induce apoptosis under extreme stress. This stress-activated response also activates endonucleases to process specific mature cytosolic mRNAs into variants that encode transcription factors. These UPR-specific transcription factors (e.g., ATF6B) increase the expression of heat shock proteins, protein disulfide isomerases, and other chaperones. The UPR exacerbates diseases caused by the expression of mutant proteins that fold incorrectly, such as cystic fibrosis and neurodegenerative disorders, or the overexpression of protein in general, such as inflammatory bowel disease, diabetic or chronic kidney disease, and nonalcoholic fatty liver disease.

QIAGEN provides a broad range of assay technologies for unfolded protein response research that enables analysis of gene expression and regulation, epigenetic modification, genotyping, and signal transduction pathway activation. Solutions optimized for unfolded protein response studies include PCR array, miRNA, siRNA, mutation analysis, pathway reporter, chromatin IP, DNA methylation, and protein expression products.