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

Biochem Biophys Res Commun. 2005 Jun 17;331(4):1146-53. doi: 10.1016/j.bbrc.2005.04.039.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA
  • DNA-Binding Proteins / physiology*
  • Endoplasmic Reticulum / metabolism*
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Nuclear Proteins / physiology*
  • Promoter Regions, Genetic
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • Transcription, Genetic / physiology*
  • X-Box Binding Protein 1

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • DNA