A Role for the Cleaved Cytoplasmic Domain of E-cadherin in the Nucleus*
- Emma C. Ferber‡,
- Mihoko Kajita‡,
- Anthony Wadlow‡,
- Lara Tobiansky‡,
- Carien Niessen§,
- Hiroyoshi Ariga¶,
- Juliet Daniel∥ and
- Yasuyuki Fujita‡**1
- ‡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
- 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.
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 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.
Footnotes
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↵2 The abbreviations used are: CH, cadherin homology; ADAM10, a disintegrin and metalloprotease 10; CBP, CREB-binding protein; E-cad/CTF, E-cadherin C-terminal fragment; HEK, human embryonic kidney; Hmat, human matrilysin; p120, p120-catenin; siRNA, short interfering RNA; CREB, cAMP-response element-binding protein; TCF/LEF-1, T-cell factor/lymphocyte enhancer factor-1; MDCK, Madin-Darby canine kidney; GST, glutathione S-transferase; HA, hemagglutinin; NLS, nuclear localization signal.
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↵3 E. C. Ferber and Y. Fujita, unpublished observation.
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Author's Choice—Final version full access.
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↵* 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.
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The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S7.
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- Received October 29, 2007.
- Revision received March 19, 2008.
- The American Society for Biochemistry and Molecular Biology, Inc.
