The SxxSS motif of T-cell factor-4 isoforms modulates Wnt/β-catenin signal activation in hepatocellular carcinoma cells
The SxxSS motif of T-cell factor-4 isoforms modulates Wnt/β-catenin signal activation in hepatocellular carcinoma cells
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.
- Brown University United States
- Rhode Island Hospital United States
Transcriptional Activation, Carcinoma, Hepatocellular, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Amino Acid Motifs, Liver Neoplasms, Molecular Sequence Data, Protein Serine-Threonine Kinases, Transfection, Wnt Proteins, Transcription Factor 4, Cell Line, Tumor, Humans, Protein Isoforms, Amino Acid Sequence, Phosphorylation, Carrier Proteins, beta Catenin, Signal Transduction, Transcription Factors
Transcriptional Activation, Carcinoma, Hepatocellular, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Amino Acid Motifs, Liver Neoplasms, Molecular Sequence Data, Protein Serine-Threonine Kinases, Transfection, Wnt Proteins, Transcription Factor 4, Cell Line, Tumor, Humans, Protein Isoforms, Amino Acid Sequence, Phosphorylation, Carrier Proteins, beta Catenin, Signal Transduction, Transcription Factors
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