Comparative Analysis of the Expression Patterns of UPR-Target Genes Caused by UPR-Inducing Compounds

• DOI: 10.1271/bbb.120812
• Publication Date: 2013-04-06T22:40:57Z
• Authors: Satoko SHINJO; Yuji MIZOTANI; Etsu TASHIRO; Masaya IMOTO
• Keywords: 0303 health sciences; Membrane Glycoproteins; Time Factors; Cell Survival; Gene Expression Profiling; 03 medical and health sciences; Unfolded Protein Response; Cluster Analysis; Humans; RNA, Messenger; Monensin; Endoplasmic Reticulum Chaperone BiP; Heat-Shock Proteins; HeLa Cells

Endoplasmic reticulum (ER) stress, due to an accumulation of unfolded proteins in the ER, leads to a process known as the unfolded protein response (UPR). Since the several compounds used to induce UPR have different modes of action, their mechanisms of protein accumulation are thought to be different, but it is unclear whether these compounds can upregulate UPR target genes with similar kinetics. Hence, we sought to compare the expression patterns of nine UPR target genes induced by seven UPR-inducing compounds. Hierarchical clustering analysis revealed that the expression patterns of the UPR target genes induced by the seven compounds were classified into two clusters; cluster A (thapsigargin, tunicamycin, 2-deoxyglucose, and dithiothreitol) and cluster B (brefeldin A, monensin, and eeyarestatin I). Thus, this study suggests the existence of at least two types of UPR target gene expression profiles, which depend on the mode of action of the compounds.