ABSTRACT
Fig. 1 Schematic representation of Wnt/b-catenin signaling cascade. A. In the absence of Wnt ligand, cytoplasmic b-catenin bound to its destruction complex consists of APC, Axin, CK1a and GSK-3b. b-Catenin is fi rst phosphorylated by CK1a followed by further phosphorylation by GSK-3b. Phosphorylated b-catenin is recognized by b-TrCP followed by degradation by the 26S proteosomal system. In the nucleus, TCF-regulated transcription of target genes is repressed by the coordinated action of CtBP, Groucho, HBP1 and HDAC. B. Following binding of Wnt to FZD and simultaneously to LRP 5/6, Dvl is recruited to FZD followed by recruitment of Axin and GSK-3b to LRP 5/6. This results in the dissociation of b-catenin destruction complex. b-Catenin is stabilized and translocates to the nucleus, where it binds to TCF/LEF in the presence of Bcl-9, CBP/p300 and Pygogus, and activates the transcription of target genes.
