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Functional interaction between Sp1 and c‐Jun in phorbol 12‐myristate 13‐acetate‐induced gene expression of cytosolic phospholipase A2α
Author(s) -
Chen BenKuen,
Wang WeiChiao,
Tzou JenHuei,
Chang WenChang
Publication year - 2006
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.20.4.a696
Subject(s) - cytosol , phorbol , phospholipase a2 , chemistry , phorbol ester , gene expression , microbiology and biotechnology , gene , protein kinase c , biochemistry , biology , enzyme
The functional role of the interaction between c‐Jun and simian virus 40 promoter factor 1 (Sp1) in 12‐myristate 13‐acetate (PMA)‐induced expression of cytosolic phospholipase A 2 α (cPLA 2 α) gene in A549 human lung adenocarcinoma cell was studied. PMA increased the expression of cPLA 2 α in a time‐dependent manner. The effect of PMA on the promoter activation of cPLA 2 α gene was analyzed by using the luciferase fusion vectors. PMA and overexpression of c‐Jun induced the promoter activity of cPLA 2 α in a dose‐ and time‐dependent manner. Transient transfection with series of 5′‐deleted constructs showed that the 5′‐flanking region spanning from −53 to −17 bp from translation starting site played an important role for PMA response. Site‐directed mutagenesis indicated that two non‐classical Sp1 binding sequences residing at −51 to −42 bp and −33 to −24 bp were responsible for the PMA and c‐Jun in activation of human cPLA 2 α gene expression. Furthermore, coimmunoprecipitation and DNA affinity precipitation assay experiments indicated that PMA stimulated interaction between c‐Jun and Sp1 in a time‐dependent manner and binding of c‐Jun/Sp1 to promoter. These results indicate that the interaction between c‐Jun and Sp1 induced by PMA cooperatively activated expression of cPLA 2 α gene.