Figure 1.

Schematic illustrating the Wnt/β-catenin pathway. (A) In the absence of a Wnt signal, β-catenin is bound to E-Cadherin (E-CAD) at adherens junctions or is phosphorylated by a destruction complex comprised of the core proteins AXIN, APC (adenomatous polyposis coli), GSK3 (glycogen synthase kinase), and CK1 (casein kinase 1). N-terminal phosphorylated β-catenin is targeted for ubiquitination and subsequent proteasomal degradation, maintaining low levels of cystosolic and nuclear β-catenin. Expression of Wnt/β-catenin target genes via activation of TCF/LEF (T-cell factor/lymphoid enhancer factor) transcription factors is inhibited by the transcriptional repressor Groucho. (B) Wnt ligand initiates signaling through FZD (Frizzled) receptor and LRP (low-density lipoprotein receptor-related protein) co-receptor, activating and recruiting DVL (Dishevelled) and Axin to the membrane, thereby disrupting the destruction complex. Higher cytosolic levels of β-catenin result in its translocation into the nucleus, where it binds TCF/LEF transcription factors and displaces Groucho to trans-activate Wnt/β-catenin target gene expression.