Defining the roles of β-catenin and plakoglobin in LEF/T-cell factor-dependent transcription using β-catenin/plakoglobin-null F9 cells

Masayuki Shimizu, Yoshitaka Fukunaga, Junichi Ikenouchi, Akira Nagafuchi

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30 Citations (Scopus)

Abstract

β-Catenin functions as a transcriptional regulator in Wnt signaling. Its function is regulated by a specific destruction system. Plakoglobin is a close homologue of β-catenin in mammalian cells and is regulated in a similar fashion. When β-catenin or plakoglobin is exogenously expressed in cells, endogenous β-catenin is stabilized, which complicates estimation of the transcriptional activities of exogenously expressed proteins. To facilitate the design of experiments aimed at investigating the transcriptional activities of β-catenin and plakoglobin, we utilized F9 cells in which we knocked out endogenous β-catenin and/or plakoglobin by gene deletion and exogenously expressed wild-type and mutant β-catenin and/or plakoglobin. We show that C-terminally deleted β-catenin, but not plakoglobin, has a strong dominant-negative eifect on transcription without altering the nuclear accumulation of β-catenin. Moreover, we show that Wnt-3a activation of LEF/T-cell factor (TCF)-dependent transcription depends on β-catenin but not on plakoglobin. Using chimeras of β-catenin and plakoglobin, we demonstrate that plakoglobin has the potential to function in transcriptional regulation but is not responsible for Wnt-3a signaling in F9 cells. Our data show that preferential nuclear accumulation of β-catenin is not necessarily linked to its transcriptional activity. We also clearly demonstrate that plakoglobin is insufficient for LEF/TCF-dependent transcriptional activation by Wnt-3a in F9 cells.

Original languageEnglish
Pages (from-to)825-835
Number of pages11
JournalMolecular and cellular biology
Volume28
Issue number2
DOIs
Publication statusPublished - Jan 1 2008

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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