A Novel β-Catenin-binding Protein Inhibits β-Catenin-dependent Tcf Activation and Axis Formation*

By I. Sakamoto, S. Kishida, A. Fukui, M. Kishida, Hideki Yamamoto, S. Hino, T. Michiue, S. Takada, Makoto Asashima, A. Kikuchi. Journal of Biological Chemistry, 2000

85 citations recorded by the source corpus.

β-Catenin is efficiently phosphorylated by glycogen synthase kinase-3β in the Axin complex in the cytoplasm, resulting in the down-regulation. In response to Wnt, β-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 β-catenin in the nucleus. Duplin was located in the nucleus. Duplin bound directly to the Armadillo repeats of β-catenin, thereby inhibiting the binding of Tcf to β-catenin. It did not affect the stability of β-catenin but inhibited Wnt- or β-catenin-dependent Tcf activation. Furthermore, expression of Duplin in Xenopus embryos inhibited the axis formation and β-catenin-dependent axis duplication, and prevented the β-catenin's ability to rescue ventralizing phenotypes induced by ultraviolet light irradiation. Thus, Duplin is a nuclear protein that inhibits β-catenin signaling.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/6db8585f9966818b751174d6a0e9e0687a8748ff