Inhibition of beta-catenin-mediated transactivation by cadherin derivatives.

Abstract:

:We studied the effect of N-cadherin, and its free or membrane-anchored cytoplasmic domain, on the level and localization of beta-catenin and on its ability to induce lymphocyte enhancer-binding factor 1 (LEF-1)-responsive transactivation. These cadherin derivatives formed complexes with beta-catenin and protected it from degradation. N-cadherin directed beta-catenin into adherens junctions, and the chimeric protein induced diffuse distribution of beta-catenin along the membrane whereas the cytoplasmic domain of N-cadherin colocalized with beta-catenin in the nucleus. Cotransfection of beta-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 beta-catenin from the nucleus to the plasma membrane and reduced transactivation. The cytoplasmic tails of N- or E-cadherin colocalized with beta-catenin in the nucleus, and suppressed the constitutive LEF-1-mediated transactivation, by blocking beta-catenin-LEF-1 interaction. Moreover, the 72 C-terminal amino acids of N-cadherin stabilized beta-catenin and reduced its transactivation potential. These results indicate that beta-catenin binding to the cadherin cytoplasmic tail either in the membrane, or in the nucleus, can inhibit beta-catenin degradation and efficiently block its transactivation capacity.

authors

Sadot E,Simcha I,Shtutman M,Ben-Ze'ev A,Geiger B

doi

10.1073/pnas.95.26.15339

subject

Has Abstract

pub_date

1998-12-22 00:00:00

pages

15339-44

issue

26

eissn

0027-8424

issn

1091-6490

journal_volume

95

pub_type

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