residues of β-catenin, BTRC promotes its ubiquitination, which causes it to be degraded by the TrCP/SKP complex. On the other hand, when Wnt is present, GSK-3B is displaced from the previously mentioned complex, causing β-catenin to not be phosphorylated, and thus not ubiquitinated. As a result, its levels in the cell are stabilized as it builds up in the cytoplasm. Eventually, some of this accumulated β-catenin will move into the nucleus with the help of Rac1. At this point, β-catenin becomes a coactivator for TCF and LEF to activate Wnt genes by displacing Groucho and HDAC transcription repressors. These gene products are important in determining cell fates during normal development and in maintaining homeostasis, or they can lead to de-regulated growth in disorders like cancer by responding to mutations in β-catenin, APC or Axin, each of which can lead to this de-regulated β-catenin level stabilization in cells. While less attention is directed at α-catenin in studies involving cell adhesion, it is nonetheless an important player in cellular organization, function and growth. α-catenin participates in the formation and stabilization of adherens junctions by binding to β-catenin-cadherin complexes in the cell. The exact mechanisms by which α-catenin acts in adherens junctions is still unclear; however, it is likely that α-catenin acts in concert with vinculin to bind to actin and help stabilize the junctions. Interaction with cadherins F9 embryonal carcinoma cells are similar to the P19 cells shown in Figure 1 and normally have cell-to-cell adhesion mediated by E-cadherin with β-catenin bound to the cytoplasmic domain of E-cadherin. F9 cells were genetically engineered to lack β-catenin, resulting in increased association of plakoglobin with E-cadherin. In F9 cells lacking both β-catenin and plakoglobin, very little E-cadherin and α-catenin accumulated at the cell surface. Mice lacking β-catenin have defective embryos. Mice engineered to specifically have vascular endothelium cells deficient in β-catenin showed disrupted adhesion between vascular endothelial cells. Mice lacking plakoglobin have cell adhesion defects in many tissues, although β-catenin substitutes for plakoglobin at many cellular junctions. Keratinocytes engineered to not express alpha-catenin have disrupted cell adhesion and activated NF-κB. A tumor cell line with defective δ-catenin, low levels of E-cadherin and poor cell-to-cell adhesion could be restored to normal epithelial morphology and increased E-cadherin levels by expression of normal levels of functional δ-catenin. Clinical significance As previously mentioned, the same properties of catenin that give it an important role in normal cell fate