NH4Cl) had no effect, but chloroquine (Fig. 6, lane 6; Chl) blocked E-cadherin degradation almost as effectively as the proteosome inhibitors. In both the PS341- and chloroquine-treated cells, cytoplasmic pools of E-cadherin increased, but the increased levels were not reflected by increased adhesion or higher surface cadherin levels. Thus, these inhibitors appear to block cadherin degradation, but do not affect internalization. The data suggest that when newly synthesized E-cadherin arrives at the cell surface, p120 is required to prevent the immediate targeting of unbound E-cadherin for degradation by the proteosome and/or lysosome. We conclude that p120 regulates cadherin turnover by controlling either internalization, or possibly an immediately subsequent decision whereby internalized cadherins are sorted into recycling or degradation pathways.
