DIFFERENTIAL NUCLEAR TRANSLOCATION AND TRANSACTIVATION POTENTIAL OF BETA-CATENIN AND PLAKOGLOBIN

beta-Catenin and plakoglobin are homologous proteins that function in cell adhesion by linking cadherins to the cytoskeleton and in signalin g by transactivation together with lymphoid-enhancing binding/T cell ( LEF/TCF) transcription factors. Here we compared the nuclear transloca tion and transactivation abilities of beta-catenin and plakoglobin in mammalian cells. Overexpression of each of the two proteins in MDCK ce lls resulted in nuclear translocation and formation of nuclear aggrega tes. The beta-catenin-containing nuclear structures also contained LEF -1 and vinculin, while plakoglobin was inefficient in recruiting these molecules, suggesting that its interaction with LEF-1 and vinculin is significantly weaker. Moreover, transfection of LEF-1 translocated en dogenous beta-catenin, but not plakoglobin to the nucleus. Chimeras co nsisting of Gal4 DNA-binding domain and the transactivation domains of either plakoglobin or beta-catenin were equally potent in transactiva ting a Gal4-responsive reporter, whereas activation of LEF-1-responsiv e transcription was significantly higher with beta-catenin. Overexpres sion of wild-type plakoglobin or mutant beta-catenin lacking the trans activation domain induced accumulation of the endogenous beta-catenin in the nucleus and LEF-1-responsive transactivation. It is further sho wn that the constitutive beta-catenin-dependent transactivation in SW4 80 colon carcinoma cells and its nuclear localization can be inhibited by overexpressing N-cadherin or alpha-catenin. The results indicate t hat (a) plakoglobin and beta-catenin differ in their nuclear transloca tion and complexing with LEF-1 and vinculin; (b) LEF-1-dependent trans activation is preferentially driven by beta-catenin; and (c) the cytop lasmic partners of beta-catenin, cadherin and alpha-catenin, can seque ster it to the cytoplasm and inhibit its transcriptional activity.