אסיף מאגר המחקר החקלאי

Inhibition of β-catenin-mediated transactivation by cadherin derivatives

Year:

1998

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Authors :

Volume :

95

Co-Authors:

Sadot, E., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
Simcha, I., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
Shtutman, M., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
Ben-Ze'ev, A., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
Geiger, B., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel

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Abstract:

We studied the effect of N-cadherin, and its free or membrane-anchored cytoplasmic domain, on the level and localization of β-catenin and on its ability to induce lymphocyte enhancer-binding factor 1 (LEF-1)-responsive transactivation. These cadherin derivatives formed complexes with β-catenin and protected it from degradation. N-cadherin directed β-catenin into adherens junctions, and the chimeric protein induced diffuse distribution of β-catenin along the membrane whereas the cytoplasmic domain of N-cadherin colocalized with β-catenin in the nucleus. Cotransfection of β-catenin and LEF-1 into Chinese hamster ovary cells induced transactivation of a LEF-1 reporter, which was blocked by the N-cadherin-derived molecules. Expression of N-cadherin and an interleukin 2 receptor/cadherin chimera in SW480 cells relocated β-catenin from the nucleus to the plasma membrane and reduced transactivation. The cytoplasmic tails of N- or E-cadherin colocalized with β-catenin in the nucleus, and suppressed the constitutive LEF-1-mediated transactivation, by blocking β-catenin-LEF-1 interaction. Moreover, the 72 C-terminal amino acids of N-cadherin stabilized β-catenin and reduced its transactivation potential. These results indicate that β-catenin binding to the cadherin cytoplasmic tail either in the membrane, or in the nucleus, can inhibit β-catenin degradation and efficiently block its transactivation capacity.

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