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 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.
Kanemoto
Soshi
S
Division of Molecular and Cellular Biology, Department of Anatomy, Faculty of Medicine, University of Miyazaki, Kihara 5200, Kiyotake, Miyazaki 889-1692, Japan.
Kondo
Shinichi
S
Ogata
Maiko
M
Murakami
Tomohiko
T
Urano
Fumihiko
F
Imaizumi
Kazunori
K
D001483:Base Sequence; D004247:DNA; D004268:DNA-Binding Proteins / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000502:physiology*; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D004247:DNA