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  Cell-Type-Specific Function of BCL9 Involves a Transcriptional Activation Domain that Synergizes with β-Catenin

Sustmann, C., Flach, H., Ebert, H., Eastman, Q., & Grosschedl, R. (2008). Cell-Type-Specific Function of BCL9 Involves a Transcriptional Activation Domain that Synergizes with β-Catenin. Molecular and Cellular Biology (Washington, DC), 28, 3526-3537. doi:10.1128/MCB.01986-07.

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Sustmann 2008_Mol Cell Biol.pdf (Publisher version), 2MB
 
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Sustmann, Claudio1, Author              
Flach, Henrik1, Author              
Ebert, Hanna1, Author              
Eastman, Quinn1, Author              
Grosschedl, Rudolf1, Author              
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1Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              

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 Abstract: Transcriptional regulation by the canonical Wnt pathway involves the stabilization and nuclear accumulation of β-catenin, which assembles with LEF1/TCF transcription factors and cofactors to activate Wnt target genes. Recently, the nuclear β-catenin complex has been shown to contain BCL9, which interacts with β-catenin and recruits Pygopus as a transcriptional coactivator. However, the presumed general functions of Pygopus and BCL9, which has been proposed to act as a scaffolding protein for Pygopus, have been challenged by the rather specific and modest developmental defects of targeted inactivations of both the Pygo1 and the Pygo2 genes. Here, we analyze the function of BCL9 in transcriptional activation by β-catenin. We find that BCL9 acts in a cell-type-specific manner and, in part, independent of Pygopus. We show that BCL9 itself contains a transcriptional activation domain in the C terminus, which functionally synergizes in lymphoid cells with the C-terminal transactivation domain of β-catenin. Finally, we identify amino acids in the transactivation domain of β-catenin that are important for its function and association with the histone acetyltransferases CBP/p300 and TRRAP/GCN5. Thus, BCL9 may serve to modulate and diversify the transcriptional responses to Wnt signaling in a cell-type-specific manner.

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Language(s): eng - English
 Dates: 2008-05
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1128/MCB.01986-07
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Title: Molecular and Cellular Biology (Washington, DC)
  Other : Mol Cell Biol
Source Genre: Journal
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Publ. Info: American Society for Microbiology (ASM)
Pages: - Volume / Issue: 28 Sequence Number: - Start / End Page: 3526 - 3537 Identifier: ISSN: 0270-7306
CoNE: https://pure.mpg.de/cone/journals/resource/954925502188