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MBC in Press, published online ahead of print May 18, 2005
Mol. Biol. Cell 10.1091/mbc.E05-02-0105

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Submitted on February 22, 2005
Revised on May 3, 2005
Accepted on May 5, 2005

Induction of Human NF-IL6{beta} by Epidermal Growth Factor Is Mediated through the p38 Signaling Pathway and CREB Activation in A431 cells

Ju-Ming Wang, Joseph T. Tseng, and Wen-Chang Chang

Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan

Monitoring Editor: Carl-Henrik Heldin

The CCAAT/enhancer binding protein {delta} (C/EBP{delta}, CRP3, CELF, NF-IL6{beta}) regulates gene expression and plays functional roles in many tissues, such as in acute phase response to inflammatory stimuli, adipocyte differentiation and mammary epithelial cell growth control. In this study, we examined the expression of human C/EBP{delta} (NF-IL6{beta}) gene by EGF stimulation in human epidermoid carcinoma A431 cells. NF-IL6{beta} was an immediate-early gene activated by the EGF-induced signaling pathways in cells. By using 5'-serial deletion reporter analysis, we showed that the region comprising the -347 to + 9 base pairs was required for EGF response of the NF-IL6{beta} promoter. This region contains putative consensus binding sequences of Sp1 and cAMP response element-binding protein (CREB). The NF-IL6{beta} promoter activity induced by EGF was abolished by mutating the sequence of CRE or Sp1 sites in the -347/+9 base pairs region. Both in vitro- and in vivo- DNA binding assay revealed that the CREB binding activity was low in EGF-starved cells while it was induced within 30 min following EGF treatment of A431 cells. However, no change in Sp1 binding activity was found by EGF treatment. Moreover, the PI3-kinase inhibitor (wortmannin) and p38MAPK inhibitor (SB203580) inhibited the EGF-induced CREB phosphorylation and the expression of NF-IL6{beta} gene in cells. We also demonstrated that CREB was involved in regulating the NF-IL6{beta} gene transcriptional activity mediated by p38MAPK. Our results suggested that PI3-kinase/p38MAPK/CREB pathway contributed to the EGF activation of NF-IL6{beta} gene expression.


Address correspondence to: Wen-Chang Chang (wcchang{at}mail.ncku.edu.tw)




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Nucleic Acids ResHome page
J.-M. Wang, C.-Y. Ko, L.-C. Chen, W.-L. Wang, and W.-C. Chang
Functional role of NF-IL6{beta} and its sumoylation and acetylation modifications in promoter activation of cyclooxygenase 2 gene
Nucleic Acids Res., January 5, 2006; 34(1): 217 - 231.
[Abstract] [Full Text] [PDF]




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