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Vol. 12, Issue 4, 1177-1188, April 2001

Cadherin Sequences That Inhibit -Catenin Signaling: A Study in Yeast and Mammalian Cells

Inbal Simcha,^* Catherine Kirkpatrick, Einat Sadot,^* Michael Shtutman,^* Gordon Polevoy, Benjamin Geiger,^* Mark Peifer,^¶# and Avri Ben-Ze'ev^*#

 ^*Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel, 76100;  Department of Biology,  Curriculum in Genetics and Molecular Biology, and  ^¶Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599-3280; and  ^§Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455

Drosophila Armadillo and its mammalian homologue -catenin are scaffolding proteins involved in the assembly of multiprotein complexes with diverse biological roles. They mediate adherens junction assembly, thus determining tissue architecture, and also transduce Wnt/Wingless intercellular signals, which regulate embryonic cell fates and, if inappropriately activated, contribute to tumorigenesis. To learn more about Armadillo/-catenin's scaffolding function, we examined in detail its interaction with one of its protein targets, cadherin. We utilized two assay systems: the yeast two-hybrid system to study cadherin binding in the absence of Armadillo/-catenin's other protein partners, and mammalian cells where interactions were assessed in their presence. We found that segments of the cadherin cytoplasmic tail as small as 23 amino acids bind Armadillo or -catenin in yeast, whereas a slightly longer region is required for binding in mammalian cells. We used mutagenesis to identify critical amino acids required for cadherin interaction with Armadillo/-catenin. Expression of such short cadherin sequences in mammalian cells did not affect adherens junctions but effectively inhibited -catenin-mediated signaling. This suggests that the interaction between -catenin and T cell factor family transcription factors is a sensitive target for disruption, making the use of analogues of these cadherin derivatives a potentially useful means to suppress tumor progression.

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These authors contributed equally to this work.

^# Corresponding authors. E-mail addresses: avri.ben-zeev{at}weizmann.ac.il (A.B.-Z.); peifer{at}unc.edu (M.P.).

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Molecular Biology of the Cell
Vol. 12, 1177-1188, April 2001
Copyright © 2001 by The American Society for Cell Biology

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