A Role for the Cleaved Cytoplasmic Domain of E-cadherin in the Nucleus

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2008 Mar 22

PMID 18356166

Citations 76

Authors

Emma C Ferber

Mihoko Kajita

Anthony Wadlow

Lara Tobiansky

Carien Niessen

Hiroyoshi Ariga

Juliet Daniel

Yasuyuki Fujita

Affiliations

Soon will be listed here.

Abstract

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.

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