Benedetti C, Fabbri M, Sitia R, Cabibbo A
Department of Molecular Pathology and Medicine, DIBIT, San Raffaele Scientific Institute, Via Olgettina 58, Milan, 20132, Italy.
Biochem Biophys Res Commun. 2000 Nov 30;278(3):530-6. doi: 10.1006/bbrc.2000.3838.
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.
内质网（ER）中未折叠蛋白的积累会激活一种称为未折叠蛋白反应（UPR）的信号通路，该通路会导致参与内质网蛋白折叠的因子的转录激活、蛋白质合成的短暂抑制以及内质网相关降解途径的上调。为了鉴定在UPR过程中受调控的新基因，我们使用了一种RNA指纹技术来分析用二硫苏糖醇（DTT）或衣霉素处理的细胞中的基因表达谱，这两种都是强烈的UPR诱导剂。我们分离出了两种在两种处理中均上调的新转录本。在不同细胞系和各种UPR诱导条件下，这些基因在UPR过程中的选择性调控得到了证实。这些研究突出了UPR过程中基因表达的有趣方面，包括hsp70家族成员的选择性下调。
