J. Cell Biol., Volume 141, Number 6, June 15, 1998 1433-1448

Differential Nuclear Translocation and Transactivation Potential of -Catenin and Plakoglobin

Inbal Simcha, Michael Shtutman, Daniela Salomon, Jacob Zhurinsky, Einat Sadot, Benjamin Geiger, and Avri Ben-Ze'ev

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel

-Catenin and plakoglobin are homologous proteins that function in cell adhesion by linking cadherins to the cytoskeleton and in signaling by transactivation together with lymphoid-enhancing binding/T cell (LEF/TCF) transcription factors. Here we compared the nuclear translocation and transactivation abilities of -catenin and plakoglobin in mammalian cells. Overexpression of each of the two proteins in MDCK cells resulted in nuclear translocation and formation of nuclear aggregates. The -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 endogenous -catenin, but not plakoglobin to the nucleus. Chimeras consisting of Gal4 DNA-binding domain and the transactivation domains of either plakoglobin or -catenin were equally potent in transactivating a Gal4-responsive reporter, whereas activation of LEF-1- responsive transcription was significantly higher with -catenin. Overexpression of wild-type plakoglobin or mutant -catenin lacking the transactivation domain induced accumulation of the endogenous -catenin in the nucleus and LEF-1-responsive transactivation. It is further shown that the constitutive -catenin-dependent transactivation in SW480 colon carcinoma cells and its nuclear localization can be inhibited by overexpressing N-cadherin or -catenin. The results indicate that (a) plakoglobin and -catenin differ in their nuclear translocation and complexing with LEF-1 and vinculin; (b) LEF-1-dependent transactivation is preferentially driven by -catenin; and (c) the cytoplasmic partners of -catenin, cadherin and -catenin, can sequester it to the cytoplasm and inhibit its transcriptional activity.

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