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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Andrews NC and Faller DV . (1991). Nucleic Acids Res., 19, 2499.
Barker N and Clevers H . (2000). Bioessays, 22, 961–965.
Barker N, Huls G, Korinek V and Clevers H . (1999). Am. J. Pathol., 154, 29–35.
Ben-Ze'ev A and Geiger B . (1998). Curr. Opin. Cell. Biol., 10, 629–639.
Caca K, Kolligs FT, Ji X, Hayes M, Qian J, Yahanda A, Rimm DL, Costa J and Fearon ER . (1999). Cell Growth Differ., 10, 369–376.
Clements WM, Wang J, Sarnaik A, Kim OJ, MacDonald J, Fenoglio-Preiser C, Groden J and Lowy AM . (2002). Cancer Res., 62, 3503–3506.
Crawford HC, Fingleton BM, Rudolph-Owen LA, Goss KJ, Rubinfeld B, Polakis P and Matrisian LM . (1999). Oncogene, 18, 2883–2891.
He TC, Chan TA, Vogelstein B and Kinzler KW . (1999). Cell, 99, 335–345.
He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B and Kinzler KW . (1998). Science, 281, 1509–1512.
Klein PS and Melton DA . (1996). Proc. Natl. Acad. Sci. USA, 93, 8455–8459.
Kodama S, Ikeda S, Asahara T, Kishida M and Kikuchi A . (1999). J. Biol. Chem., 274, 27682–27688.
Koh TJ, Bulitta CJ, Fleming JV, Dockray GJ, Varro A and Wang TC . (2000). J. Clin. Invest., 106, 533–539.
Kolligs FT, Kolligs B, Hajra KM, Hu G, Tani M, Cho KR and Fearon ER . (2000). Genes Dev., 14, 1319–1331.
Moon RT, Bowerman B, Boutros M and Perrimon N . (2002). Science, 296, 1644–1646.
Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B and Kinzler KW . (1997). Science, 275, 1787–1790.
Polakis P . (2000). Genes Dev., 14, 1837–1851.
Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E and Polakis P . (1997). Science, 275, 1790–1792.
Rubinfeld B, Souza B, Albert I, Munemitsu S and Polakis P . (1995). J. Biol. Chem., 270, 5549–5555.
Salomon D, Sacco PA, Roy SG, Simcha I, Johnson KR, Wheelock MJ and Ben-Ze'ev A . (1997). J. Cell Biol., 139, 1325–1335.
Satoh S, Daigo Y, Furukawa Y, Kato T, Miwa N, Nishiwaki T, Kawasoe T, Ishiguro H, Fujita M, Tokino T, Sasaki Y, Imaoka S, Murata M, Shimano T, Yamaoka Y and Nakamura Y . (2000). Nat. Genet., 24, 245–250.
Sekido Y, Bader SA, Carbone DP, Johnson BE and Minna JD . (1994). Cancer Res., 54, 4988–4992.
Shigemitsu K, Sekido Y, Usami N, Mori S, Sato M, Horio Y, Hasegawa Y, Bader SA, Gazdar AF, Minna JD, Hida T, Yoshioka H, Imaizumi M, Ueda Y, Takahashi M and Shimokata K . (2001). Oncogene, 20, 4249–4257.
Shtutman M, Zhurinsky J, Simcha I, Albanese C, D'Amico M, Pestell R and Ben-Ze'ev A . (1999). Proc. Natl. Acad. Sci. USA, 96, 5522–5527.
Sparks AB, Morin PJ, Vogelstein B and Kinzler KW . (1998). Cancer Res., 58, 1130–1134.
Stambolic V, Ruel L and Woodgett JR . (1996). Curr. Biol., 6, 1664–1668.
Tetsu O and McCormick F . (1999). Nature, 398, 422–426.
Ueda M, Gemmill RM, West J, Winn R, Sugita M, Tanaka N, Ueki M and Drabkin HA . (2001). Br. J. Cancer, 85, 64–68.
Usami N, Sekido Y, Maeda O, Yamamoto K, Minna JD, Hasegawa Y, Yoshioka H, Imaizumi M, Ueda Y, Takahashi M and Shimokata K . (2003). Oncogene, 22, 7922–7930.
Webster MT, Rozycka M, Sara E, Davis E, Smalley M, Young N, Dale TC and Wooster R . (2000). Genes Chromosomes Cancer, 28, 443–453.
Williams BO, Barish GD, Klymkowsky MW and Varmus HE . (2000). Oncogene, 19, 5720–5728.
Winn RA, Bremnes RM, Bemis L, Franklin WA, Miller YE, Cool C and Heasley LE . (2002). Oncogene, 21, 7497–7506.
Wong CM, Fan ST and Ng IO . (2001). Cancer, 92, 136–145.
Zhurinsky J, Shtutman M and Ben-Ze'ev A . (2000). Mol. Cell Biol., 20, 4238–4252.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1207254
Keywords
This article is cited by
-
Amplification of R-spondin1 signaling induces granulosa cell fate defects and cancers in mouse adult ovary
Oncogene (2017)
-
γ-Catenin acts as a tumor suppressor through context-dependent mechanisms in colorectal cancer
International Journal of Colorectal Disease (2017)
-
Inherited desmosomal disorders
Cell and Tissue Research (2015)
-
β-catenin promotes the type I IFN synthesis and the IFN-dependent signaling response but is suppressed by influenza A virus-induced RIG-I/NF-κB signaling
Cell Communication and Signaling (2014)
-
Plakoglobin as a Regulator of Desmocollin Gene Expression
Journal of Investigative Dermatology (2013)