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- Title
Plakoglobin (?-catenin) has TCF/LEF family-dependent transcriptional activity in ß-catenin-deficient cell line.
- Authors
Maeda, Osamu; Usami, Noriyasu; Kondo, Masashi; Takahashi, Masahide; Goto, Hidemi; Shimokata, Kaoru; Kusugami, Kazuo; Sekido, Yoshitaka
- Abstract
ß-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 (?-catenin), a closely related homologue of ß-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 ß-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 ß-catenin. Exogenous plakoglobin was also shown to promote entrance of exogenous ß-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 ß-catenin, and that plakoglobin has multiple functions as a transcriptional activator and a cell adhesion molecule like ß-catenin.Oncogene (2004) 23, 964-972. doi:10.1038/sj.onc.1207254 Published online 8 December 2003
- Subjects
GENES; CELL adhesion; CELL adhesion molecules; TRANSCRIPTION factors; T cells; LYMPHOCYTES
- Publication
Oncogene, 2004, Vol 23, Issue 4, p964
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1207254