In most epithelial cell lines, p120 is abundant and its close relatives such as ARVCF and δ-catenin are poorly expressed or absent. Although p120 knockdown was sufficient to nearly eliminate E-cadherin in several epithelial cell lines tested, the effect was incomplete in cells such as the colon carcinoma cell line HCT116. An obvious explanation is that p120 family members might partially or completely substitute for p120, depending on their relative abundance. Indeed, HCT116 cells are unusual in that they express moderate levels of ARVCF (unpublished data). To determine whether other p120 relatives can also regulate E-cadherin turnover, we transiently expressed GFP-labeled ARCVF or δ-catenin in A431 cells that lack p120 as a result of siRNA knockdown (Fig. 4). As a negative control, we also tested plakophilin-3, a more distant p120 relative that binds desmosomal (but not classical) cadherins. A431 cells expressing p120 siRNA alone were almost completely E-cadherin negative (Fig. 4, i and ii), as described earlier in this paper, and were not affected by GFP expression (Fig. 4 i, fluorescent cells). ARVCF (Fig. 4, iii) and δ-catenin (Fig. 4,