A role for the cleaved cytoplasmic domain of E-cadherin in the nucleus

J Biol Chem. 2008 May 9;283(19):12691-700. doi: 10.1074/jbc.M708887200. Epub 2008 Mar 19.


Cell-cell contacts play a vital role in intracellular signaling, although the molecular mechanisms of these signaling pathways are not fully understood. E-cadherin, an important mediator of cell-cell adhesions, has been shown to be cleaved by gamma-secretase. This cleavage releases a fragment of E-cadherin, E-cadherin C-terminal fragment 2 (E-cad/CTF2), into the cytosol. Here, we study the fate and function of this fragment. First, we show that coexpression of the cadherin-binding protein, p120 catenin (p120), enhances the nuclear translocation of E-cad/CTF2. By knocking down p120 with short interfering RNA, we also demonstrate that p120 is necessary for the nuclear localization of E-cad/CTF2. Furthermore, p120 enhances and is required for the specific binding of E-cad/CTF2 to DNA. Finally, we show that E-cad/CTF2 can regulate the p120-Kaiso-mediated signaling pathway in the nucleus. These data indicate a novel role for cleaved E-cadherin in the nucleus.

MeSH terms

  • Active Transport, Cell Nucleus
  • Amyloid Precursor Protein Secretases / metabolism
  • Animals
  • Apoptosis
  • Cadherins / chemistry*
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Catenins
  • Cell Adhesion Molecules / metabolism
  • Cell Nucleus / metabolism*
  • Chlorocebus aethiops
  • Cytoplasm / metabolism*
  • DNA / metabolism
  • Delta Catenin
  • Dogs
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Humans
  • Mice
  • Phosphoproteins / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Protein Structure, Tertiary
  • Staurosporine / pharmacology
  • Transcription, Genetic / genetics


  • Cadherins
  • Catenins
  • Cell Adhesion Molecules
  • Phosphoproteins
  • DNA
  • Amyloid Precursor Protein Secretases
  • Staurosporine
  • Delta Catenin