title: P120 catenin represses transcriptional activity through Kaiso in endothelial cells.
abstract: P120 catenin (p120ctn) belongs to the family of Armadillo repeat-containing proteins, which are believed to have dual functions of cell-cell adhesion and transcriptional regulation. In vascular endothelium, p120ctn is mostly recognized for its cell-cell adhesion function through its ability to regulate VE-cadherin. The current study investigated whether p120ctn in endothelial cells also has the capability to signal transcription events. Examination of several endothelial cell types indicated that Kaiso, a p120ctn-binding transcription factor, was abundantly expressed, with a predominant localization to the perinuclear region. Immunoprecipitation of endothelial cell lysates with a p120ctn antibody resulted in p120ctn-Kaiso complex formation, confirming the interactions of the two proteins. Transfection of the KBS (Kaiso-binding sequence) luciferase reporter plasmid into endothelial cells resulted in a 40% lower reporter activity compared to the mutant Kaiso-insensitive construct or empty vector pGL3, indicating that the suppressed reporter activity was attributed to endogenous Kaiso. The knock-down of p120ctn increased the KBS reporter activity 2-fold over control, but had no effects on the mutant KBS reporter activity. Furthermore, p120ctn knock-down also reduced Kaiso expression, suggesting that p120ctn functioned to stabilize Kaiso. Overall, the findings provide evidence that in endothelial cells, p120ctn has a transcription repression function through regulation of Kaiso, possibly as a cofactor with the transcription factor.
authors.affiliation: Center for Cardiovascular Sciences, Albany Medical Center, Albany, NY, USA.
authors.forename: Jihang
authors.initials: J
authors.lastname: Zhang
authors.forename: James J
authors.initials: JJ
authors.lastname: O'Donnell
authors.forename: Oksana
authors.initials: O
authors.lastname: Holian
authors.forename: Peter A
authors.initials: PA
authors.lastname: Vincent
authors.forename: Kwang S
authors.initials: KS
authors.lastname: Kim
authors.forename: Hazel
authors.initials: H
authors.lastname: Lum
mesh_terms: D000818:Animals; D051177:Catenins / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000095002:Delta Catenin
chemical_list: D051177:Catenins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C492254:ZBTB33 protein, human; D000095002:Delta Catenin
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