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The Dual Role of Cytoskeletal Anchor Proteins in Cell Adhesion and Signal Transduction
Author(s) -
BENZE'EV AVRI
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb09398.x
Subject(s) - plakoglobin , transactivation , microbiology and biotechnology , nuclear localization sequence , catenin , beta catenin , vinculin , chemistry , transcription factor , cadherin , transfection , biology , signal transduction , cytoplasm , cell , biochemistry , wnt signaling pathway , gene , focal adhesion
A bstract : β‐Catenin and plakoglobin are homologous proteins having a dual role in cell adhesion and in transactivation together with LEF/TCF transcription factors. Overexpression of plakoglobin suppresses tumorigenicity, whereas increased β‐catenin levels are considered oncogenic. We compared the nuclear translocation and transactivation by β‐catenin and plakoglobin. Overexpression of each protein resulted in nuclear translocation and formation of structures that also contained LEF‐1 and vinculin with β‐catenin, but not with plakoglobin. Transfection of LEF‐1 translocated endogenous β‐catenin, but not plakoglobin into the nucleus. Chimeras of the Gal4 DNA‐binding domain and the transactivation domains of either plakoglobin or β‐catenin were equally potent in transactivation, but induction of LEF‐1‐responsive transcription was higher with β‐catenin. Overexpression of wt plakoglobin or mutant β‐catenin lacking the transactivation domain induced nuclear accumulation of the enodogenous β‐catenin and LEF‐1‐responsive transactivation. The nuclear localization and constitutive β‐catenin‐dependent transactivation in SW480 cancer cells were inhibited by overexpressing cadherin or α‐catenin. Moreover, transfecting the cytoplasmic tail of cadherin inhibited transactivation, by competition with LEF‐1 in the nucleus for β‐catenin binding. The results indicate that (1) plakoglobin and β‐catenin differ in nuclear translocation and complexing with LEF‐1 and vinculin, (2) LEF‐1‐dependent transactivation is mainly driven by β‐catenin, (3) cadherin and α‐catenin can sequester β‐catenin, inhibit its transcriptional activity, and antogonize its oncogenic action.