DKK1, a negative regulator of Wnt signaling, is a target of the beta-catenin/TCF pathway

Oncogene. 2004 Nov 4;23(52):8520-6. doi: 10.1038/sj.onc.1207892.

Abstract

Wnt signaling plays an important role in embryonic development and tumorigenesis. These biological effects are exerted by activation of the beta-catenin/TCF transcription complex and consequent regulation of a set of downstream genes. TCF-binding elements have been found in the promoter regions of many TCF target genes and characterized by a highly conserved consensus sequence. Utilizing this consensus sequence, we performed an in silico screening for new TCF target genes. Through computational screening and subsequent experimental analysis, we identified a novel TCF target gene, DKK1, which has been shown to be a potent inhibitor of Wnt signaling. Our finding suggests the existence of a novel feedback loop in Wnt signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Computational Biology
  • Cytoskeletal Proteins / metabolism*
  • Drosophila Proteins / metabolism
  • Feedback, Physiological / physiology
  • Gene Expression Regulation / physiology
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Mice
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Proteins / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Repressor Proteins / metabolism
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism*
  • Wnt Proteins
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • Cytoskeletal Proteins
  • DKK1 protein, human
  • Dkk1 protein, mouse
  • Drosophila Proteins
  • Intercellular Signaling Peptides and Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors
  • Wnt Proteins
  • beta Catenin
  • pan protein, Drosophila