Abstract
T-cell factor (TCF) proteins represent key transcription factors in Wnt signaling. We show that the SxxSS motif in TCF-4 regulates transcriptional activity in HCC cells. TCF-4K mutants increased transcriptional activity compared to TCF-4K (bearing the SxxSS); the binding pattern of co-factors in TCF-4K mutants was similar to that in TCF-4J (lacking the SxxSS). TCF activity in TCF-4K cells was suppressed by homeodomain-interacting protein kinase 2 (HIPK2), but not in TCF-4J cells. Together, our data indicates that the SxxSS motif in TCF-4K regulates transcriptional activity by modifying co-factors in the β-catenin/TCF-4 transcriptional complex and these events may be mediated through HIPK2.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amino Acid Motifs*
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Amino Acid Sequence
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / metabolism*
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Carrier Proteins / metabolism
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Cell Line, Tumor
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Humans
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Liver Neoplasms / genetics
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Liver Neoplasms / metabolism*
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Molecular Sequence Data
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Phosphorylation
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Protein Isoforms
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Protein Serine-Threonine Kinases / metabolism
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Signal Transduction
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Transcription Factor 4
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcriptional Activation
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Transfection
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Wnt Proteins / genetics
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Wnt Proteins / metabolism*
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beta Catenin / genetics
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beta Catenin / metabolism*
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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CTNNB1 protein, human
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Carrier Proteins
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Protein Isoforms
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TCF4 protein, human
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Transcription Factor 4
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Transcription Factors
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Wnt Proteins
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beta Catenin
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HIPK2 protein, human
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Protein Serine-Threonine Kinases