Truncated AMER1 mutants destabilize the destruction complex

Stable Identifier
Reaction [transition]
Homo sapiens
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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).

Literature References
PubMed ID Title Journal Year
19760609 WTX inactivation is a frequent, but late event in Wilms tumors without apparent clinical impact

Gessler, M, Geissinger, E, Wittmann, S, Wegert, J, Leuschner, I, Graf, N

Genes Chromosomes Cancer 2009
21248786 Wilms' tumours: about tumour suppressor genes, an oncogene and a chameleon gene

Huff, V

Nat. Rev. Cancer 2011
17510365 Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling

Berndt, JD, Major, MB, Maccoss, MJ, Yi, X, Camp, ND, Biechele, TL, Hubbert, C, Gingras, AC, Angers, S, Zheng, N, Goldenberg, SJ, Moon, RT

Science 2007
18311776 Wilms tumor genetics: mutations in WT1, WTX, and CTNNB1 account for only about one-third of tumors

Huff, V, Ruteshouser, EC, Robinson, SM

Genes Chromosomes Cancer 2008
Normal reaction
Functional status

Loss of function of truncated AMER1 mutants [cytosol]

Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
kidney cancer DOID:263 malignant neoplasm of kidney except pelvis, malignant tumour of kidney, renal cancer
nephroblastoma DOID:2154 adult renal Wilms' tumor, adult nephroblastoma, childhood renal Wilms' cancer, renal Wilms tumor
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