Truncated AMER1 mutants destabilize the destruction complex

Stable Identifier
R-HSA-4839746
Type
Reaction [FailedReaction]
Species
Homo sapiens
Compartment
cytosol
Locations in the PathwayBrowser
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Summation

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

Huff, V

Nat. Rev. Cancer 2011
19760609 WTX inactivation is a frequent, but late event in Wilms tumors without apparent clinical impact

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

Genes Chromosomes Cancer 2009
17510365 Wilms tumor suppressor WTX negatively regulates WNT/beta-catenin signaling

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

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

Ruteshouser, EC, Robinson, SM, Huff, V

Genes Chromosomes Cancer 2008
Participants
Input
Participant Of
hasEvent
Disease
Name Identifier Synonyms
kidney cancer 263 malignant neoplasm of kidney except pelvis, malignant tumour of kidney, renal cancer
cancer 162 malignant tumor, malignant neoplasm, primary cancer
nephroblastoma 2154 adult renal Wilms' tumor, adult nephroblastoma, childhood renal Wilms' cancer, renal Wilms tumor
Authored
Rothfels, K  (2013-10-30)
Reviewed
Salahshor, S  (2014-05-12)
Woodgett, J  (2014-05-22)