Human CCAAT/enhancer-binding protein β gene expression is activated by endoplasmic reticulum stress through an unfolded protein response element downstream of the protein coding sequence

Chin Chen, Elizabeth E. Dudenhausen, Yuan Xiang Pan, Can Zhong, Michael S. Kilberg

Research output: Contribution to journalArticlepeer-review

Abstract

CCAAT/enhancer-binding protein β (C/EBPβ) is a member of the bZIP family of transcription factors that contribute to the regulation of a wide range of important cellular processes. The data in the present study document that transcription from the human C/EBPβ gene is induced in response to endoplasmic reticulum stress, such as glucose deprivation, or treatment of cells with tunicamycin or thapsigargin. Transient transfection of C/EBPβ genomic fragments linked to a luciferase reporter gene demonstrated that the C/EBPβ BP13 promoter plays no major regulatory role. Instead, by deletion analysis it was discovered that a 46-bp region, located at a genomic site that corresponds to the 3′-untranslated region of tine C/EBPβ mRNA, harbored an element that was required for the stress response. Mutagenesis demonstrated that a cis-regulatory element located at nt +1614-1621 (5′-TGACGCAA-3′) is responsible for activation of the C/EBPβ gene. Electrophoresis mobility shift analysis revealed that proteins are bound to this element and that the amount of binding is increased following glucose deprivation. This element is homologous to a previously reported mammalian unfolded protein response element that binds XBP-1. Consistent with those data, overexpression of XBP-1 caused an increase in transcription that was mediated by the C/EBPβ mammalian unfolded protein response element.

Original languageEnglish (US)
Pages (from-to)27948-27956
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number27
DOIs
StatePublished - Jul 2 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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