| First Author | Tu YC | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 12 | Pages | e84062 |
| PubMed ID | 24386331 | Mgi Jnum | J:211121 |
| Mgi Id | MGI:5574129 | Doi | 10.1371/journal.pone.0084062 |
| Citation | Tu YC, et al. (2013) Regulation of c-Fos gene expression by NF-kappaB: a p65 homodimer binding site in mouse embryonic fibroblasts but not human HEK293 cells. PLoS One 8(12):e84062 |
| abstractText | 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)-kappaB is also required for controlling c-Fos expression is unclear. In this study, we determined how NF-kappaB'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)-alpha did not. In mouse embryonic fibroblasts, the PMA induction of c-Fos was suppressed by a deficiency in IKKalpha, IKKbeta, IKKgamma, 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-kappaB binding site in the mouse but not human c-fos promoter. Under PMA stimulation, IKKalpha/beta mediated p65 phosphorylation and the binding of the p65 homodimer to the NF-kappaB site in the mouse c-fos promoter. Furthermore, our studies demonstrated independent but coordinated functions of the IKKalpha/beta-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-kappaB for mouse and human c-fos regulation. Binding of the p65 homodimer to the kappaB site was indispensable for mouse c-fos expression, whereas the kappaB 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-alpha induces c-Fos more weakly than PMA does in both mouse and human cells. |
