Fig. (3).

(a) “Off State”. In the absence of Wnt signals, β-catenin is captured by a degradation complex containing Gsk3 (glycogen synthase kinase 3), Axin/Conductin, CK1 (casein kinase 1) and APC (adenomatous polyposis coli) where it is first phosphorylated and then ubiquitinated on N-terminal sequences by β-TrCP (β-transducin repeat-containing protein). β-catenin is subsequently targeted for proteasomal degradation. In the nucleus, the transcriptional inhibitor TLE (human homolog of Drosophila Groucho) binds to LEF/TCF (lymphoid enhancer factor/T-cell factor) and inhibits transcription. (b) “On State”. Wnts bind to and activate FZD (Frizzled) and LRP (LDL-related receptor protein) receptors on target cells. LRP5/LRP6 are phosphorylated by CK1 and Gsk3, and DVL (Dishevelled) molecules are recruited to the plasma membrane to interact with FZD. The interaction of Axin with phosphorylated LRP5/6 and DVL leads to the inactivation of the degradation complex and the accumulation of β-catenin, which translocates to the nucleus. In the nucleus, β-catenin forms a transcriptionally active complex with LEF and TCF by displacing Groucho and interacts with co-activators such as BCL9 (B-cell lymphoma 9), Pygo (Pygopus), CBP (CREB-binding protein) and MLL (mixed-lineage leukemia).