I. Sakamoto et al., A novel beta-catenin-binding protein inhibits beta-catenin-dependent Tcf activation and axis formation, J BIOL CHEM, 275(42), 2000, pp. 32871-32878
beta -Catenin is efficiently phosphorylated by glycogen synthase kinase-3 b
eta 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. I
t did not affect the stability of beta -catenin but inhibited Wnt- or beta
-catenin-dependent Tcf activation. Furthermore, expression of Duplin in Xen
opus embryos inhibited the axis formation and beta -catenin-dependent axis
duplication, and prevented the beta -catenin's ability to rescue ventralizi
ng phenotypes induced by ultraviolet light irradiation. Thus, Duplin is a n
uclear protein that inhibits beta -catenin signaling.