Proteasome inhibitors activate the transcription factors C/EBP-β and δ in human intestinal epithelial cells

Eric S. Hungness, Bruce W. Robb, Guang Ju Luo, Timothy A. Pritts, Dan D. Hershko, Per Olof Hasselgren

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

In recent studies, induction of the heat shock response by hyperthermia upregulated the expression and DNA binding activity of the transcription factor C/EBP. This is an important observation because it may at least in part explain why the heat shock response upregulates IL-6 production in the intestinal mucosa and in the enterocyte. A novel method to induce the heat shock response is proteasome inhibition. The influence of this treatment on the expression and DNA binding activity of C/EBP is not known. We treated cultured Caco-2 cells, a human intestinal epithelial cell line, with one of the proteasome inhibitors, MG-132 or lactacystin, and measured C/EBP-β and δ DNA binding activity by electrophoretic mobility shift assay and supershift analysis. In addition, nuclear levels of C/EBP-β and δ protein were determined by Western blot analysis. Treatment of the cells with the proteasome inhibitors resulted in increased cellular levels of heat shock protein 72, consistent with induction of the heat shock response. Treatment also resulted in increased DNA binding activity and nuclear protein levels of C/EBP-β and δ. The effects of the proteasome inhibitors on C/EBP were inhibited by treating the cells with quercetin, a substance known to block the heat shock response. The results suggest that proteasome inhibition activates the transcription factors C/EBP-β and δ in human intestinal epithelial cells and that this response, at least in part, is caused by induction of the heat shock response. The observations are important because they provide support for a novel method to influence gene activation in the enterocyte.

Original languageEnglish (US)
Article number96168
Pages (from-to)469-474
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume290
Issue number1
DOIs
StatePublished - Jan 1 2002

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Heat-Shock Response
Proteasome Inhibitors
Transcription Factors
Epithelial Cells
CCAAT-Enhancer-Binding Proteins
Enterocytes
DNA
Proteasome Endopeptidase Complex
HSP72 Heat-Shock Proteins
Electrophoretic mobility
Caco-2 Cells
Quercetin
DNA-Binding Proteins
Electrophoretic Mobility Shift Assay
Intestinal Mucosa
Nuclear Proteins
Transcriptional Activation
Hot Temperature
Cultured Cells
Interleukin-6

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Proteasome inhibitors activate the transcription factors C/EBP-β and δ in human intestinal epithelial cells. / Hungness, Eric S.; Robb, Bruce W.; Luo, Guang Ju; Pritts, Timothy A.; Hershko, Dan D.; Hasselgren, Per Olof.

In: Biochemical and Biophysical Research Communications, Vol. 290, No. 1, 96168, 01.01.2002, p. 469-474.

Research output: Contribution to journalArticle

Hungness, Eric S. ; Robb, Bruce W. ; Luo, Guang Ju ; Pritts, Timothy A. ; Hershko, Dan D. ; Hasselgren, Per Olof. / Proteasome inhibitors activate the transcription factors C/EBP-β and δ in human intestinal epithelial cells. In: Biochemical and Biophysical Research Communications. 2002 ; Vol. 290, No. 1. pp. 469-474.
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