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

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 m...

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Bibliographic Details
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
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2005.04.039