Abstract
Elucidation of the cellular signaling pathways that contribute to cancer development often begins with the identification of a gene mutated in human tumors. Complementary biochemical approaches become especially important when the sequence of the newly identified gene provides few clues as to its function. Major et al . used analysis of protein interaction networks to define the function of WTX , a tumor suppressor gene found very recently to be mutated in an inherited kidney cancer called Wilms tumor. The WTX protein forms a complex with several proteins in the Wnt signaling cascade, including β-catenin, Axin1, β-TRCP2 (β-transducin repeat-containing protein 2), and APC (adenomatous polyposis coli), and antagonizes Wnt signaling by promoting β-catenin degradation. M. B. Major, N. D. Camp, J. D. Berndt, X. Yi, S. J. Goldenberg, C. Hubbert, T. L. Biechele, A.-C. Gingras, N. Zheng, M. J. MacCoss, S. Angers, R. T. Moon, Wilms tumor suppressor WTX negatively regulates WNT/β-catenin signaling. Science 316 , 1043-1046 (2007). [Abstract] [Full Text] R. Nusse, Converging on β-catenin in Wilms tumor. Science 316 , 988-989 (2007). [Summary] [Full Text]
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