Nucleic Acids Research Advance Access first published online on November 19, 2007
This version published online on December 11, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm1027
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Molecular Biology |
Nucleolin regulates c-Jun/Sp1-dependent transcriptional activation of cPLA2
in phorbol ester-treated non-small cell lung cancer A549 cells
1Department of Pharmacology, 2Department of Internal Medicine, College of Medicine, 3Center for Gene Regulation and Signal Transduction and 4Institute of Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan
*To whom correspondence should be addressed. Tel: +886 6 235 3535 Ext. 5496; Fax: +886 6 274 9296; Email: bkchen58{at}mail.ncku.edu.tw
Received July 13, 2007. Revised October 16, 2007. Accepted October 29, 2007.
The expression of cPLA2 is critical for transformed growth of non-small cell lung cancer (NSCLC). It is known that phorbol 12-myristate 13-acetate (PMA)-activated signal transduction pathway is thought to be involved in the oncogene action in NSCLC and enzymatic activation of cPLA2. However, the transcriptional regulation of cPLA2
in PMA-activated NSCLC is not clear. In this study, we found that PMA induced the mRNA level and protein expression of cPLA2
. In addition, two Sp1-binding sites of cPLA2
promoter were required for response to PMA and c-Jun overexpression. Small interfering RNA (siRNA) of c-Jun and nucleolin inhibited PMA induced the promoter activity and protein expression of cPLA2
. Furthermore, PMA stimulated the formation of c-Jun/Sp1 and c-Jun/nucleolin complexes as well as the binding of these transcription factor complexes to the cPLA2
promoter. Although Sp1-binding sites were required for the bindings of Sp1 and nucleolin to the promoter, the binding of nucleolin or Sp1 to the promoter was independent of each other. Our results revealed that c-Jun/nucleolin and c-Jun/Sp1 complexes play an important role in PMA-regulated cPLA2
gene expression. It is likely that nucleolin binding at place of Sp1 on gene promoter could also mediate the regulation of c-Jun/Sp1-activated genes.