beta-Catenin and plakoglobin N- and C-tails determine ligand specificity

The Journal of Biological Chemistry
Guiomar SolanasM Dunach

Abstract

beta-Catenin and plakoglobin are related proteins involved in the regulation of adherens junctions and desmosomes. Moreover, by binding to Tcf-4, they can act as transcriptional modulators of genes involved in embryonic development and tumorigenesis. However, they associate to distinct Tcf-4 subdomains causing opposing effects on Tcf-4 binding to DNA: whereas beta-catenin does not affect this binding, plakoglobin prevents it. Both proteins are composed by two N- and C-tails and a central armadillo repeat domain. Interaction of Tcf-4, as well as other desmosomal or adherens junction components, with beta-catenin or plakoglobin takes place through the central armadillo domain. Here we show that, as reported for beta-catenin, plakoglobin terminal tails also interact with the central domain and regulate the ability of this region to bind to different cofactors. Moreover the specificity of the interaction of beta-catenin and plakoglobin with different subdomains in Tcf-4 or with other junctional components resides within the terminal tails and not in the armadillo domain. For instance, a chimeric protein in which the central domain of beta-catenin was replaced by that of plakoglobin presented the same specificity as wild-type beta-c...Continue Reading

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Citations

Mar 16, 2005·Biochemical and Biophysical Research Communications·Purba BiswasJoseph A Madri
Jul 18, 2008·Human Molecular Genetics·Mark LalMichael J Caplan
Dec 30, 2006·Molecular and Cellular Biology·Julio CastañoMireia Duñach
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