The fact that p120 availability limits cadherin levels has several crucial implications. For example, overexpression of dominant-negative cadherins frequently down-regulates expression of endogenous cadherins (Kintner, 1992; Fujimori and Takeichi, 1993; Zhu and Watt, 1996), but the mechanism is unknown. Our data strongly suggest that a key action of dominant-negative cadherins is the sequestering of endogenous p120, thereby driving the turnover and degradation of endogenous cadherins. In addition, cadherin levels in cells may ultimately be controlled by factors that regulate p120 levels, and competition for interaction with p120 is likely to be physiologically relevant in cells that express more than one cadherin.
