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J. Biol. Chem., Vol. 283, Issue 19, 12691-12700, May 9, 2008
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**1
From the
MRC Cell Biology Unit, MRC Laboratory for Molecular Cell Biology, **Department of Cell and Developmental Biology, University College London, London, WC1E 6BT, United Kingdom, the
Department of Dermatology, Center for Molecular Medicine Cologne, University of Cologne, Joseph Stelzmannstrasse 9, 50931 Cologne, Germany, the ¶Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo 060-0812, Japan, and the ||Department of Biology, LSB-331, McMaster University, Hamilton, Ontario L8S 4K1, Canada
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
-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.
Received for publication, October 29, 2007 , and in revised form, March 19, 2008.
Author's Choice—Final version full access.
* This work was supported by Medical Research Council funding to the Cell Biology Unit. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S7.
Author's Choice
1 To whom correspondence should be addressed. Tel.: 44-20-7679-7208; Fax: 44-20-7679-7805; E-mail: y.fujita{at}ucl.ac.uk.
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