1DUMMY Regulation of c-Fos gene expression by NF-κB: A p65 homodimer binding site in mouse embryonic fibroblasts but not human HEK293 cells

Yu Cheng Tu, Duen Yi Huang, Shine Gwo Shiah, Jang Shiun Wang, Wan Wan Lin

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The immediate early gene c-Fos is reported to be regulated by Elk-1 and cAMP response element-binding protein (CREB), but whether nuclear factor (NF)-κB is also required for controlling c-Fos expression is unclear. In this study, we determined how NF-κB's coordination with Elk/serum response factor (SRF) regulates c-fos transcription. We report that PMA strongly induced c-Fos expression, but tumor necrosis factor (TNF)-α did not. In mouse embryonic fibroblasts, the PMA induction of c-Fos was suppressed by a deficiency in IKKα, IKKβ, IKKγ, or p65. By contrast, in human embryonic kidney 293 cells, PMA induced c-Fos independently of p65. In accordance with these results, we identified an NF-κB binding site in the mouse but not human c-fos promoter. Under PMA stimulation, IKKα/β mediated p65 phosphorylation and the binding of the p65 homodimer to the NF-κB site in the mouse c-fos promoter. Furthermore, our studies demonstrated independent but coordinated functions of the IKKα/β-p65 and extracellular signal-regulated kinase (ERK)-Elk-1 pathways in the PMA induction of c-Fos. Collectively, these results reveal the distinct requirement of NF-κB for mouse and human c-fos regulation. Binding of the p65 homodimer to the κB site was indispensable for mouse c-fos expression, whereas the κB binding site was not present in the human c-fos promoter. Because of an inability to evoke sufficient ERK activation and Elk-1 phosphorylation, TNF-α induces c-Fos more weakly than PMA does in both mouse and human cells.

Original languageEnglish
Article numbere84062
JournalPLoS One
Volume8
Issue number12
DOIs
Publication statusPublished - Dec 30 2013

Fingerprint

IKappaB kinase
fos Genes
Phosphorylation
HEK293 Cells
Extracellular Signal-Regulated MAP Kinases
Fibroblasts
Gene expression
fibroblasts
binding sites
Tumor Necrosis Factor-alpha
elks
Binding Sites
Serum Response Factor
Gene Expression
Cyclic AMP Response Element-Binding Protein
gene expression
mice
Transcription
tumor necrosis factors
Genes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

1DUMMY Regulation of c-Fos gene expression by NF-κB : A p65 homodimer binding site in mouse embryonic fibroblasts but not human HEK293 cells. / Tu, Yu Cheng; Huang, Duen Yi; Shiah, Shine Gwo; Wang, Jang Shiun; Lin, Wan Wan.

In: PLoS One, Vol. 8, No. 12, e84062, 30.12.2013.

Research output: Contribution to journalArticle

Tu, Yu Cheng ; Huang, Duen Yi ; Shiah, Shine Gwo ; Wang, Jang Shiun ; Lin, Wan Wan. / 1DUMMY Regulation of c-Fos gene expression by NF-κB : A p65 homodimer binding site in mouse embryonic fibroblasts but not human HEK293 cells. In: PLoS One. 2013 ; Vol. 8, No. 12.
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