Physiological and functional interactions between Tcf4 and Daxx in colon cancer cells.
Daxx, a human cell death-associated protein, was isolated as a Tcf4-interacting protein, using a yeast two-hybrid screen. Co-immunoprecipitation in HEK-293T cells and yeast two-hybrid screen in Y190 cells were performed to identify the interaction between Tcf4 with Daxx and to map the binding regions of Tcf4. In the nucleus, Daxx reduced DNA binding activity of Tcf4 and repressed Tcf4 transcriptional activity. Overexpression of Daxx altered the expression of genes downstream of Tcf4, including cyclin D1 and Hath-1, and induced G1 phase arrest in colon cancer cells. A reduction in Daxx protein expression was also observed in colon adenocarcinoma tissue when compared with normal colon tissue. This evidence suggests a possible physiological function of Daxx, via interaction with Tcf4, to regulate proliferation and differentiation of colon cells.
Institute of Toxicology, Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Shu-Ling
SL
Tzeng
Yu-Wen
YW
Cheng
Ching-Hao
CH
Li
Young-Sun
YS
Lin
Hey-Chi
HC
Hsu
Jaw-Jou
JJ
Kang
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001665:Binding Sites; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056970:Co-Repressor Proteins; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase; D015870:Gene Expression; D019940:Genes, bcl-1; D006801:Humans; D066298:In Vitro Techniques; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D051820:TCF Transcription Factors / Q000235:genetics / Q000502:physiology*; D058118:Transcription Factor 7-Like 2 Protein; D020798:Two-Hybrid System Techniques; D051176:beta Catenin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; D056970:Co-Repressor Proteins; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D051820:TCF Transcription Factors; D058118:Transcription Factor 7-Like 2 Protein; D051176:beta Catenin; C106985:DAXX protein, human; C544894:TCF7L2 protein, human