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Stabilization of [beta]‐catenin by cPLA2[alpha]‐mediated activation of PPAR[delta]
Author(s) -
Han Chang,
Lim Kyu,
Xu Lihong,
Li Guiying,
Wu Tong
Publication year - 2008
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.22.1_supplement.1124.8
Subject(s) - chemistry , peroxisome proliferator activated receptor , catenin , response element , microbiology and biotechnology , phospholipase a2 , signal transduction , cytosol , receptor , wnt signaling pathway , biochemistry , biology , enzyme , promoter , gene expression , gene
Cytosolic phospholipase A2α (cPLA2α) is a rate‐limiting key enzyme that releases arachidonic acid (AA) from membrane phospholipids. This study shows a novel role of cPLA2α for activation of peroxisome proliferator‐activated receptor‐δ (PPARδ) and β‐catenin in the nuclei. Overexpression of cPLA2α in human cholangiocarcinoma cells induced the binding of PPARδ to β‐catenin and increased their association with the TCF/LEF response element. These effects are inhibited by the cPLA2α siRNA and inhibitors as well as by siRNA knockdown of PPARδ. Overexpression of PPARδ or treatment with the selective PPARδ ligand, GW501516, also increased β‐catenin binding to TCF/LEF response element and increased its reporter activity. Addition of AA and GW501516 to nuclear extracts induced a comparable degree of β‐catenin binding to TCF/LEF response element. Furthermore, cPLA2α protein is present in the PPARδ and β‐catenin binding complex, suggesting that PPARδ may direct the import of cPLA2α into the nucleus. Thus the close proximity between cPLA2α and PPARδ provides a unique advantage for their efficient functional coupling in the nucleus, where AA produced by cPLA2α becomes immediately available for PPARδ binding and subsequent β‐catenin activation. These results depict a novel interaction linking cPLA2α, PPARδ and Wnt/β‐catenin signaling pathways in human cells.