Daxx positively modulates beta-catenin/TCF4-mediated transcriptional potential.
Constitutive activation of the transcription factor TCF4 activity by mutated APC or beta-catenin contributes to cell neoplastic transformation. While numerous proteins were identified to activate TCF4-dependent activity via beta-catenin interaction, little is known about factors directly acting on TCF4. Here we report that Daxx binds to TCF4 and potentiates beta-catenin/TCF4-mediated transcriptional activation and target gene expression. Binding studies revealed that Daxx-TCF4 interaction is through the C-terminal domain of Daxx and TCF4 segment containing amino acid residue 269-327. Alteration of Daxx levels in cells by overexpression or RNA interference resulted in an increase or decrease of the beta-catenin/TCF4-dependent transactivation activity and target gene expression, respectively. Furthermore, TCF4-(269-327) segment acts as a dominantly negative mutant by blocking Daxx-TCF4 interaction and TCF4-mediated transactivation potential. Together, our results suggest that Daxx functions as a positive coregulator in modulating the beta-catenin/TCF4-dependent transcriptional potential via TCF4 interaction.
Huang
Yen-Sung
YS
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
Shih
Hsiu-Ming
HM
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D047468:Immunoprecipitation; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C495270:CTNNB1 protein, human; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D004268:DNA-Binding Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051176:beta Catenin