XBP1 activates the transcription of its target genes via an ACGT core sequence under ER stress

• Published in: Biochemical and biophysical research communications 2005-06, Vol.331 (4), p.1146-1153
• Main Authors: Kanemoto, Soshi, Kondo, Shinichi, Ogata, Maiko, Murakami, Tomohiko, Urano, Fumihiko, Imaizumi, Kazunori
• Format: Article
• Language: English
• Subjects: ACGT core; Base Sequence; cis-element; DNA; DNA-Binding Proteins - physiology; Endoplasmic Reticulum - metabolism; ER stress; HeLa Cells; Humans; IRE1; Molecular Sequence Data; Nuclear Proteins - physiology; Promoter Regions, Genetic; Regulatory Factor X Transcription Factors; Transcription; Transcription Factors; Transcription, Genetic - physiology; UPR; X-Box Binding Protein 1; XBP1
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.04.039

In mammals, the transmembrane protein kinase/endoribonuclease IRE1 is activated by endoplasmic reticulum stress and subsequently processes XBP1 mRNA to generate an active form of XBP1 protein. The spliced form of XBP1 protein acts as a transcription factor and induces the expression of ER-resident molecular chaperones. However, the mechanism for how XBP1 promotes the transcription of its target genes as well as the cis-acting elements for XBP1 during ER stress has been unclear. Recently, it was demonstrated that the expression of MDG1/ERdj4, a member of the DnaJ family, is regulated by the IRE1-XBP1 pathway. In the present report, we investigated the regulatory mechanisms of MDG1/ERdj4 gene expression by XBP1. We identified a cis-acting element in the MDG1/ERdj4 promoter region, to which XBP1 specifically binds in response to ER stress. Our results reveal a target sequence for the IRE1-XBP1 pathway under ER stress conditions.