Plakoglobin (gamma-catenin) has TCF/LEF family-dependent transcriptional activity in beta-catenin-deficient cell line.
Beta-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 (gamma-catenin), a closely related homologue of beta-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 beta-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 beta-catenin. Exogenous plakoglobin was also shown to promote entrance of exogenous beta-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 beta-catenin, and that plakoglobin has multiple functions as a transcriptional activator and a cell adhesion molecule like beta-catenin.
Maeda
Osamu
O
Department of Internal Medicine, Nagoya University School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya 466-8560, Japan.
Usami
Noriyasu
N
Kondo
Masashi
M
Takahashi
Masahide
M
Goto
Hidemi
H
Shimokata
Kaoru
K
Kusugami
Kazuo
K
Sekido
Yoshitaka
Y
D001483:Base Sequence; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000502:physiology*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D051180:Desmoplakins; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D011233:Precipitin Tests; D034741:RNA, Small Interfering; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D051176:beta Catenin; D051185:gamma Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D051180:Desmoplakins; C495292:JUP protein, human; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D034741:RNA, Small Interfering; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D051185:gamma Catenin