FIGURE 6.

Model. In unstimulated cells (−Wnt), APC associated with Axin in the β-catenin destruction complex is conjugated with K63-linked polyubiquitin. This modification could either enforce APC's interaction with Axin (Interaction 1*) or facilitate the recruitment of β-TrCP to phosphorylated β-catenin for its K48-ubiquitylation and 26S proteasomal degradation (Interaction 2). Following Wnt stimulation (+Wnt), a reciprocal loss and gain of K63-polyubiquitin on APC and Dvl, respectively, could facilitate the recruitment of Axin-GSK3β to Dvl/LRP signalosomes (*), and the signalosome complex may subsequently be internalized to multi-vesicular bodies (MVB) for processing (9, 32, 59, 60). Unphosphorylated β-catenin associated with APC might conceivably be targeted to peripheral membrane pools (3, 43–47), and the free β-catenin pool enters the nucleus to activate TCF-dependent transcription (61). Fzd, Frizzled; LRP, low-density lipoprotein receptor-related protein 5/6; TLE, transducin-like enhancer of split (transcriptional co-repressor).