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Plakoglobin (γ-catenin) has TCF/LEF family-dependent transcriptional activity in β-catenin-deficient cell line

Abstract

β-Catenin is an essential element for the transcriptional activation of target genes in the Wnt signaling cascade and is also a cell adhesion molecule that couples with cadherins. Although plakoglobin (γ-catenin), a closely related homologue of β-catenin, is also known to be a cell adhesion molecule, its function as a transcriptional factor has not been revealed in detail. Using a human malignant mesothelioma cell line, NCI-H28, in which we have identified a homozygous deletion of the β-catenin gene, we studied whether plakoglobin has a T-cell factor/lymphocyte enhancer factor (TCF/LEF) family-dependent transcriptional activity. Transfection with the wild-type plakoglobin expression vector induced accumulation of plakoglobin in the nucleus. Immunoprecipitation assay with cotransfection of plakoglobin and either TCF-4 or LEF-1 detected binding of plakoglobin to TCF-4 or LEF-1. Luciferase reporter assay demonstrated transcriptional activity of the wild-type plakoglobin when transfected with TCF/LEF, although plakoglobin showed less activity than β-catenin. Exogenous plakoglobin was also shown to promote entrance of exogenous β-catenin into the nuclei. Furthermore, small interfering RNA directed against plakoglobin suppressed expression of endogenous plakoglobin and its transcriptional activity, suggesting that endogenous plakoglobin has a weak transcriptional activity. These results suggest that plakoglobin can activate the Wnt signaling cascade directly without interaction of β-catenin, and that plakoglobin has multiple functions as a transcriptional activator and a cell adhesion molecule like β-catenin.

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Acknowledgements

We thank Dr Bert Vogelstein for providing pGL3-OT and pGL3-OF, Dr Adi F Gazdar for the NCI-H1299 cell line, Dr Noriaki Sunaga and Dr John D Minna for useful comments and providing Tax siRNA, and Ms Hiroko Kako and Ms Yumie Matsushita for technical support.

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Correspondence to Yoshitaka Sekido.

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Maeda, O., Usami, N., Kondo, M. et al. Plakoglobin (γ-catenin) has TCF/LEF family-dependent transcriptional activity in β-catenin-deficient cell line. Oncogene 23, 964–972 (2004). https://doi.org/10.1038/sj.onc.1207254

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