Gan, X.Q., Wang, J.Y., Xi, Y., Wu, Z.L., Li, Y.P., and Li, L. (2008) Nuclear Dvl, c-Jun, beta-catenin, and TCF form a complex leading to stabilization of beta-catenin-TCF interaction. The Journal of cell biology. 180(6):1087-1100.
In canonical Wnt signaling, Dishevelled (Dvl) is a critical cytoplasmic regulator that releases beta-catenin from degradation. Here, we find that Dvl and c-Jun form a complex with beta-catenin-T-cell factor 4 (TCF-4) on the promoter of Wnt target genes and regulate gene transcription. The complex forms via two interactions of nuclear Dvl with c-Jun and beta-catenin, respectively, both of which bind to TCF. Disrupting the interaction of Dvl with either c-Jun or beta-catenin suppresses canonical Wnt signaling-stimulated transcription, and the reduction of Dvl diminished beta-catenin-TCF-4 association on Wnt target gene promoters in vivo. Expression of a TCF-Dvl fusion protein largely rescued the c-Jun knockdown Wnt signaling deficiency in mammalian cells and zebrafish. Thus, we confirm that c-Jun functions in canonical Wnt signaling and show that c-Jun functions as a scaffold in the bet Expression of a TCF-Dvl fusion protein largely rescued the c-Jun knockdown Wnt signaling deficiency in mammalian cells and zebrafish. Thus, we cona-catenin-TCFs transcription complex bridging Dvl to TCF. Our results reveal a mechanism by which nuclear Dvl cooperates with c-Jun to regulate gene transcription stimulated by the canonical Wnt signaling pathway.