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

Research output: Contribution to journalArticle

108 Citations (Scopus)

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

Fingerprint

gamma Catenin
TCF Transcription Factors
Catenins
Lymphocytes
Cell Line
Cell Adhesion Molecules
Gene Deletion
Cadherins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Maeda, Osamu ; Usami, Noriyasu ; Kondo, Masashi ; Takahashi, Masahide ; Goto, Hidemi ; Shimokata, Kaoru ; Kusugami, Kazuo ; Sekido, Yoshitaka. / Plakoglobin (γ-catenin) has TCF/LEF family-dependent transcriptional activity in β-catenin-deficient cell line. In: Oncogene. 2004 ; Vol. 23, No. 4. pp. 964-972.
@article{274ad4a00f8c4508a2cfb36cffc714e1,
title = "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. 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.",
author = "Osamu Maeda and Noriyasu Usami and Masashi Kondo and Masahide Takahashi and Hidemi Goto and Kaoru Shimokata and Kazuo Kusugami and Yoshitaka Sekido",
year = "2004",
month = "1",
day = "29",
doi = "10.1038/sj.onc.1207254",
language = "English",
volume = "23",
pages = "964--972",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "4",

}

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, vol. 23, no. 4, pp. 964-972. https://doi.org/10.1038/sj.onc.1207254

Plakoglobin (γ-catenin) has TCF/LEF family-dependent transcriptional activity in β-catenin-deficient cell line. / Maeda, Osamu; Usami, Noriyasu; Kondo, Masashi; Takahashi, Masahide; Goto, Hidemi; Shimokata, Kaoru; Kusugami, Kazuo; Sekido, Yoshitaka.

In: Oncogene, Vol. 23, No. 4, 29.01.2004, p. 964-972.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Plakoglobin (γ-catenin) has TCF/LEF family-dependent transcriptional activity in β-catenin-deficient cell line

AU - Maeda, Osamu

AU - Usami, Noriyasu

AU - Kondo, Masashi

AU - Takahashi, Masahide

AU - Goto, Hidemi

AU - Shimokata, Kaoru

AU - Kusugami, Kazuo

AU - Sekido, Yoshitaka

PY - 2004/1/29

Y1 - 2004/1/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=1342343924&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1342343924&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1207254

DO - 10.1038/sj.onc.1207254

M3 - Article

C2 - 14661054

AN - SCOPUS:1342343924

VL - 23

SP - 964

EP - 972

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 4

ER -