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

beta -Catenin is efficiently phosphorylated by glycogen synthase kinase-3 beta 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.