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Negative cooperativity between juxtaposed E-box and cAMP/TPA responsive elements in the cholecystokinin gene promoter

I J Rourke, T V Hansen, C Nerlov, J F Rehfeld, F C Nielsen

17 Citations (Scopus)

Abstract

The promoter of the cholecystokinin (CCK) gene possesses evolutionary conserved juxtaposed E-box and cAMP/TPA responsive elements (CRE/TRE). We have examined the functional interaction of these two sites. As previously noted, c-Jun/c-Fos heterodimers greatly increase promoter activity through association with the CRE/TRE. Mutation of the E-box enhanced the activation by c-Jun/c-Fos, as well as stimulation by forskolin and bFGF, that acts through the CRE/TRE site. Moreover, c-Jun/c-Fos stimulation was inhibited by co-expression of c-Myc and Max. The results indicate that factors associating with the E-box exhibit a negative cooperative effect on the activation via the CRE/TRE element. We propose that this mechanism plays a significant role in CCK gene transcription and other genes with juxtaposed E-box and CRE/TRE.

Original languageEnglish
JournalFEBS Letters
Volume448
Issue number1
Pages (from-to)15-8
Number of pages4
ISSN0014-5793
DOIs
Publication statusPublished - 1 Apr 1999
Externally publishedYes

Keywords

  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Basic-Leucine Zipper Transcription Factors
  • Cholecystokinin/genetics
  • Cyclic AMP/metabolism
  • Cyclic AMP Response Element-Binding Protein/genetics
  • DNA-Binding Proteins/genetics
  • Gene Expression Regulation
  • Helix-Loop-Helix Motifs
  • Humans
  • Leucine Zippers
  • Mice
  • Molecular Sequence Data
  • Mutagenesis
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-fos/genetics
  • Proto-Oncogene Proteins c-jun/genetics
  • Proto-Oncogene Proteins c-myc/genetics
  • Response Elements
  • Tetradecanoylphorbol Acetate/metabolism
  • Transcription Factors/genetics
  • Tumor Cells, Cultured

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