A role for the cleaved cytoplasmic domain of E-cadherin in the nucleus

被引:117
作者
Ferber, Emma C. [1 ]
Kajita, Mihoko [1 ]
Wadlow, Anthony [1 ]
Tobiansky, Lara [1 ]
Niessen, Carien [3 ]
Ariga, Hiroyoshi [4 ]
Daniel, Juliet [5 ]
Fujita, Yasuyuki [1 ,2 ]
机构
[1] UCL, MRC Cell Biol Unit, MRC Lab Mol Cell Biol, London WC1E 6BT, England
[2] UCL, Dept Cell & Dev Biol, London WC1E 6BT, England
[3] Univ Cologne, Dept Dermatol, Ctr Mol Med Cologne, D-50931 Cologne, Germany
[4] Hokkaido Univ, Grad Sch Pharmaceut Sci, Kita Ku, Sapporo, Hokkaido 0600812, Japan
[5] McMaster Univ, Dept Biol, Hamilton, ON L8S 4K1, Canada
基金
英国医学研究理事会;
关键词
D O I
10.1074/jbc.M708887200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:12691 / 12700
页数:10
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