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

Osamu Maeda, Noriyasu Usami, Masashi Kondo, Masahide Takahashi, Hidemi Goto, Kaoru Shimokata, Kazuo Kusugami, Yoshitaka Sekido

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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. Transaction 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.

Original languageEnglish
Pages (from-to)964-972
Number of pages9
JournalOncogene
Volume23
Issue number4
DOIs
Publication statusPublished - 29-01-2004

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Maeda, O., Usami, N., Kondo, M., Takahashi, M., Goto, H., Shimokata, K., Kusugami, K., & Sekido, Y. (2004). Plakoglobin (γ-catenin) has TCF/LEF family-dependent transcriptional activity in β-catenin-deficient cell line. Oncogene, 23(4), 964-972. https://doi.org/10.1038/sj.onc.1207254