A novel beta-catenin-binding protein inhibits beta-catenin-dependent Tcf activation and axis formation.

beta-Catenin is efficiently phosphorylated by glycogen synthase kinase-3beta in the Axin complex in the cytoplasm, resulting in the down-regulation. In response to Wnt, beta-catenin is stabilized and translocated into the nucleus where it stimulates gene expression through Tcf/Lef. Here we report a novel protein, designated Duplin (for axis duplication inhibitor), ...
which negatively regulates the function of beta-catenin in the nucleus. Duplin was located in the nucleus. Duplin bound directly to the Armadillo repeats of beta-catenin, thereby inhibiting the binding of Tcf to beta-catenin. It did not affect the stability of beta-catenin but inhibited Wnt- or beta-catenin-dependent Tcf activation. Furthermore, expression of Duplin in Xenopus embryos inhibited the axis formation and beta-catenin-dependent axis duplication, and prevented the beta-catenin's ability to rescue ventralizing phenotypes induced by ultraviolet light irradiation. Thus, Duplin is a nuclear protein that inhibits beta-catenin signaling.
Mesh Terms:
Amino Acid Sequence, Animals, Body Patterning, COS Cells, Cadherins, Calcium-Calmodulin-Dependent Protein Kinases, Carrier Proteins, Cell Line, Cell Nucleus, Cytoskeletal Proteins, Embryo, Nonmammalian, Glycogen Synthase Kinase 3, Glycogen Synthase Kinases, L Cells, Mice, Molecular Sequence Data, Nuclear Proteins, Recombinant Proteins, Spodoptera, TCF Transcription Factors, Trans-Activators, Transcription Factor 7-Like 2 Protein, Transcription Factors, Transfection, Xenopus Proteins, Xenopus laevis, beta Catenin
J Biol Chem
Date: Oct. 20, 2000
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