title: The SxxSS motif of T-cell factor-4 isoforms modulates Wnt/β-catenin signal activation in hepatocellular carcinoma cells.
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.
authors.affiliation: Liver Research Center, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Tomimaru
authors.forename: Hironori
authors.initials: H
authors.lastname: Koga
authors.forename: Tai Ho
authors.initials: TH
authors.lastname: Shin
authors.forename: Chelsea Q
authors.initials: CQ
authors.lastname: Xu
authors.forename: Jack R
authors.initials: JR
authors.lastname: Wands
authors.forename: Miran
authors.initials: M
authors.lastname: Kim
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C495270:CTNNB1 protein, human; D002352:Carrier Proteins; D020033:Protein Isoforms; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; C115114:HIPK2 protein, human; D017346:Protein Serine-Threonine Kinases
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