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).
Gessler, M, Geissinger, E, Wittmann, S, Wegert, J, Leuschner, I, Graf, N
Huff, V
Berndt, JD, Major, MB, Maccoss, MJ, Yi, X, Camp, ND, Biechele, TL, Hubbert, C, Gingras, AC, Angers, S, Zheng, N, Goldenberg, SJ, Moon, RT
Huff, V, Ruteshouser, EC, Robinson, SM
Loss of function of truncated AMER1 mutants [cytosol]
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