Mutations in exon 3 of the beta-catenin gene have been identified in a number of human cancers (Morin et al, 1997; Rubinfeld et al, 1997; reviewed in Polakis, 2000; Polakis, 2007). These mutations generally affect serine and threonine residues (S33, S37, T41, S45) that are the sites of phosphorylation by CK1 and GSK3; phosphorylation of these residues is required for the ubiquitin-mediated degradation of beta-catenin. Hence mutation of these phospho-acceptor sites stabilizes beta-catenin, allowing it to accumulate, translocate to the nucleus and activate WNT signaling through association with LEF1/TCF DNA binding partners (Hart et al, 1999; Peifer and Polakis, 2000; Laurent-Puig et al, 2001; reviewed in Saito-Diaz et al, 2013).
Laurent-Puig, P, Legoix, P, Bluteau, O, Belghiti, J, Franco, D, Binot, F, Monges, G, Thomas, G, Bioulac-Sage, P, Zucman-Rossi, J
Rubinfeld, B, Robbins, P, El-Gamil, M, Albert, I, Porfiri, E, Polakis, P
Morin, PJ, Sparks, AB, Korinek, V, Barker, N, Clevers, HC, Vogelstein, B, Kinzler, KW
Peifer, M, Polakis, P
Saito-Diaz, K, Chen, TW, Wang, X, Thorne, CA, Wallace, HA, Page-McCaw, A, Lee, E
Hart, MJ, de los Santos, R, Albert, IN, Rubinfeld, B, Polakis, P
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