Aspects of gene regulation during the UPR in human cells

The accumulation of unfolded proteins in the endoplasmic reticulum (ER) activates a signaling pathway known as the unfolded protein response (UPR), which leads to the transcriptional activation of factors involved in ER protein folding, to a transitory inhibition of protein synthesis and to an upregulation of the ER-associated degradation pathway. In order to identify new genes regulated during the UPR we have used an RNA fingerprinting technique to analyze the gene expression profiles in cells treated with DTT or tunicamycin, two strong UPR inducers. We isolated two novel transcripts upregulated by both treatments. The selective regulation of these genes during the UPR was confirmed in different cell lines and under various UPR-inducing conditions. These studies highlighted interesting aspects of the gene expression during the UPR, including a selective downregulation of members of the hsp70 family.