A role for the cleaved cytoplasmic domain of E-cadherin in the nucleus.
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.
Ferber
Emma C
EC
University College London, London, WC1E 6BT, UK.
Kajita
Mihoko
M
Wadlow
Anthony
A
Tobiansky
Lara
L
Niessen
Carien
C
Ariga
Hiroyoshi
H
Daniel
Juliet
J
Fujita
Yasuyuki
Y
D021581:Active Transport, Cell Nucleus; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D019311:Staurosporine / Q000494:pharmacology; D014158:Transcription, Genetic / Q000235:genetics; D000095002:Delta Catenin
D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; D004247:DNA; D053829:Amyloid Precursor Protein Secretases; D019311:Staurosporine; D000095002:Delta Catenin