Destruction of the β-catenin (β-Cat) destructor Axin. (A) β-catenin is phosphorylated by the Axin complex containing GSK3, CKIα and APC. Phosphorylated β-catenin is recognized by β-Trcp, an ubiquitin ligase, and degraded by the ubiquitination/proteasome pathway. (B) Wnt stimulation inhibits β-catenin phosphorylation/destruction, leading to increased β-catenin protein (which then enters the nucleus to activate transcription). (C) TNKS binds to and promotes the destruction of Axin, likely through Axin PARsylation. As such, β-catenin stabilization occurs. (D) XAV939 and IWR-1 bind to and inhibit TNKS, and therefore stabilize Axin and enhance β-catenin destruction. IWR-1 may also bind to and stabilize Axin.