title: Differential nuclear translocation and transactivation potential of beta-catenin and plakoglobin.
abstract: beta-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 beta-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 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 endogenous beta-catenin, but not plakoglobin to the nucleus. Chimeras consisting of Gal4 DNA-binding domain and the transactivation domains of either plakoglobin or beta-catenin were equally potent in transactivating a Gal4-responsive reporter, whereas activation of LEF-1- responsive transcription was significantly higher with beta-catenin. Overexpression of wild-type plakoglobin or mutant beta-catenin lacking the transactivation domain induced accumulation of the endogenous beta-catenin in the nucleus and LEF-1-responsive transactivation. It is further shown that the constitutive beta-catenin-dependent transactivation in SW480 colon carcinoma cells and its nuclear localization can be inhibited by overexpressing N-cadherin or alpha-catenin. The results indicate that (a) plakoglobin and beta-catenin differ in their nuclear translocation and complexing with LEF-1 and vinculin; (b) LEF-1-dependent transactivation is preferentially driven by beta-catenin; and (c) the cytoplasmic partners of beta-catenin, cadherin and alpha-catenin, can sequester it to the cytoplasm and inhibit its transcriptional activity.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Simcha
authors.forename: M
authors.initials: M
authors.lastname: Shtutman
authors.forename: D
authors.initials: D
authors.lastname: Salomon
authors.forename: J
authors.initials: J
authors.lastname: Zhurinsky
authors.forename: E
authors.initials: E
authors.lastname: Sadot
authors.forename: B
authors.initials: B
authors.lastname: Geiger
authors.forename: A
authors.initials: A
authors.lastname: Ben-Ze'ev
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051180:Desmoplakins; D004285:Dogs; D015870:Gene Expression; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D014452:Ubiquitins / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin
chemical_list: C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; C495272:Ctnna1 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051180:Desmoplakins; C052130:GAL4 protein, S cerevisiae; C497573:LEF1 protein, human; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D009097:Multienzyme Complexes; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014452:Ubiquitins; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin; D016596:Vinculin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex