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 γ-secretase. This cleavage releases a fragment of E-cadhe...

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Published inThe Journal of biological chemistry Vol. 283; no. 19; pp. 12691 - 12700
Main Authors Ferber, Emma C., Kajita, Mihoko, Wadlow, Anthony, Tobiansky, Lara, Niessen, Carien, Ariga, Hiroyoshi, Daniel, Juliet, Fujita, Yasuyuki
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 09.05.2008
American Society for Biochemistry and Molecular Biology
Subjects
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
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
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Summary: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 γ-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.
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ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M708887200