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Adherens junction protein, p120 catenin, represses transcriptional activity of endothelial cells
Author(s) -
Lum Hazel,
Cheng Feng,
O'Donnell James J.,
Im Heejeong,
Holian Oksana
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1028.3
Subject(s) - adherens junction , microbiology and biotechnology , transfection , reporter gene , gene silencing , transcription factor , signal transduction , chemistry , biology , cell , cadherin , cell culture , gene , gene expression , biochemistry , genetics
The adherens junction‐associated protein, p120 catenin (p120ctn) belongs to the family of armadillo repeat containing proteins which harbor dual functions of cell‐cell adhesion and signaling to the nucleus. In endothelium, while p120ctn is most characterized for cell‐cell adhesion, virtually nothing is known of this latter function. We investigated whether p120ctn in endothelial cells has signaling function to the nucleus with use of minimal promoter reporter systems. Results show that siRNA‐mediated silencing of endogenous p120ctn increased luciferase activity 1.5‐2.0‐fold in cells transfected with reporter plasmids containing binding elements for transcription factors NF κ B (pNF κ B‐Luc,) or AP‐1 (pAP‐1‐Luc). The 120ctn loss also significantly increased promoter reporter activity of pro‐inflammatory genes, MMP‐1 [p(‐562)MMP‐1‐Luc]and ICAM‐1 [p(‐1393)ICAM‐1‐Luc]. The increased promoter reporter activity was accompanied by activation of ERK1/2 as detected by anti‐phospho‐ERK1/2(Thr202/Tyr204) Ab. Further, inhibition of ERK1/2 with MEK1 inhibitor (PD 98059) prevented nuclear translocation of endogenous p65 subunit of NF κ B as well as the increased luciferase activity of p(‐562)MMP‐1‐Luc. In conclusion, loss of p120ctn was a potent stimulus of transcriptional activity, suggesting a novel transcription repression function by endothelial cells. The study is supported by NIH HL093715.