Deletions of the AMER1 gene prevent expression of AMER1 protein

Genomic deletions of the entire AMER1/WTX gene occur in about 12% of Wilms tumors, a pediatric kidney cancer. Nonsense and missense mutations have also been identified (Ruteshouser et al, 2008; Wegert et al, 2009). AMER1 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).

在整个AMER1/WTX基因的基因组缺失在约12%的威尔姆斯瘤中发生，这是一种儿童肾癌。非编码和错义突变亦已被发现（Ruteshouser等人，2008；Wegert等人，2009）。AMER1已知为破坏复合体的组分，并通过C端直接与β-连环蛋白相互作用（Major等人，2007）。在哺乳动物细胞中通过siRNA耗竭AMER1可稳定细胞中β-连环蛋白的水平，并增加β-连环蛋白依赖性报告基因的表达，这表明AMER1是一种肿瘤抑制基因（Major等人，2007；参见Huff，2011年的综述）。