AMER1/WTX is a known component of the destruction complex and interacts directly with beta-catenin through the C-terminal half (Major et al, 2007). siRNA depletion of AMER1 in mammalian cells stabilizes cellular beta-catenin levels and increases the expression of a beta-catenin-dependent reporter gene, suggesting that AMER1 is a tumor suppressor gene (Major et al, 2007; reviewed in Huff, 2011). Consistent with this, nonsense and missense mutations that truncate AMER1 and result in loss of the beta-catenin binding region have been identified in Wilms tumor, a pediatric kidney cancer (Ruteshouser et al, 2008; Wegert et al, 2009).