TGF-β signaling regulates DACT1 expression in intestinal epithelial cells

Biomed Pharmacother. 2018 Jan:97:864-869. doi: 10.1016/j.biopha.2017.11.017. Epub 2017 Nov 7.

Abstract

DACT1, was first identified as a Dishevelled-associated antagonist of Wnt signaling pathway. It has been reported that DACT1 functions in embryonic development and tumorigenesis. However, the regulation of DACT1 still remains unclear. We found Wnt signaling has no effect on DACT1, but TGF-β increases expression of DACT1 in intestinal epithelial cells. In addition, the minimal promoter is located in the region of -500bp to +1bp and the region between -3000bp to +1bp enhanced promoter activity. Site-directed mutation analysis was performed and indicated that potential regulatory elements was near -335bp. Our study provided the basic information for the exploration of DACT1 regulation and expression. Moreover, TGF-β inhibits Wnt signaling to enhance the function of DACT1 inhibiting Wnt signaling.

Keywords: DACT1; TGF-β; Transcriptional regulation; Wnt signaling.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Epithelial Cells / metabolism*
  • Gene Expression Regulation
  • Humans
  • Intestinal Mucosa / cytology
  • Mutagenesis, Site-Directed
  • Nuclear Proteins / genetics*
  • Promoter Regions, Genetic
  • Rats
  • Transforming Growth Factor beta / metabolism*
  • Wnt Signaling Pathway*

Substances

  • Adaptor Proteins, Signal Transducing
  • DACT1 protein, human
  • Dact1 protein, rat
  • Nuclear Proteins
  • Transforming Growth Factor beta