We studied the effect of N-cadherin, and its free or membrane-anchored cyto
plasmic domain, on the level and localization of beta-catenin and on its ab
ility to induce lymphocyte enhancer-binding factor 1 (LEF-1)-responsive tra
nsactivation. These cadherin derivatives formed complexes with beta-catenin
and protected it from degradation. N-cadherin directed beta-catenin into a
dherens junctions, and the chimeric protein induced diffuse distribution of
beta-catenin along the membrane whereas the cytoplasmic domain of N-cadher
in colocalized with beta-catenin in the nucleus. Cotransfection of beta-cat
enin and LEE-1 into Chinese hamster ovary cells induced transactivation of
a LEE-1 reporter, which was blocked by the N-cadherin-derived molecules. Ex
pression of N-cadherin and an interleukin 2 receptor/cadherin chimera in SW
480 cells relocated beta-catenin from the nucleus to the plasma membrane an
d reduced transactivation, The cytoplasmic tails of N- or E-cadherin coloca
lized with beta-catenin in the nucleus, and suppressed the constitutive LEE
-1-mediated transactivation, by blocking beta-catenin-LEF-1 interaction. Mo
reover, the 72 C-terminal amino acids of N-cadherin stabilized beta-catenin
and reduced its transactivation potential. These results indicate that bet
a-catenin binding to the cadherin cytoplasmic tail either in the membrane,
or in the nucleus, can inhibit beta-catenin degradation and efficiently blo
ck its transactivation capacity.