TY - JOUR
T1 - P120 catenin represses transcriptional activity through Kaiso in endothelial cells
AU - Zhang, Jihang
AU - O'Donnell, James J.
AU - Holian, Oksana
AU - Vincent, Peter A.
AU - Kim, Kwang S.
AU - Lum, Hazel
N1 - Funding Information:
This work was supported by National Heart Lung and Blood Institute Grant HL093715 (HL).
PY - 2010/9
Y1 - 2010/9
N2 - 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.
AB - 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.
KW - Armadillo repeat-containing proteins
KW - Endothelial cells
KW - Kaiso
KW - P120 catenin
KW - Transcription repression
KW - VE-cadherin
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UR - http://www.scopus.com/inward/citedby.url?scp=77955431289&partnerID=8YFLogxK
U2 - 10.1016/j.mvr.2010.04.001
DO - 10.1016/j.mvr.2010.04.001
M3 - Article
C2 - 20382170
AN - SCOPUS:77955431289
SN - 0026-2862
VL - 80
SP - 233
EP - 239
JO - Microvascular Research
JF - Microvascular Research
IS - 2
ER -