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]