C/EBP is an essential component of PDGFRA transcription in MG-63 cells.
Interleukin-1beta (IL-1beta) is a potent inhibitor of platelet-derived growth factor alpha receptor (PDGFRalpha) expression in MG-63 cells. Its effect is mediated at the transcriptional level, but the transcription factors involved in this process are unknown. In the current study, we found that IL-1beta could inhibit the PDGFRalpha gene promoter activity, and this effect was strongly correlated with increased binding of CCAAT/enhancer-binding protein (C/EBP) to the responsive promoter region. In addition, forced expression of C/EBPbeta could mimic the IL-1beta effect on the promoter activity, but subsequent mutation analysis of the C/EBP binding sites indicated that direct C/EBP binding to the promoter is not required for the IL-1beta response. However, our data clearly demonstrated that the C/EBP binding site at position-162 relative to the transcriptional start site is essential for high basal level PDGFRalpha promoter activity.
Afink
Gijs
G
Department of Cell Biology, University of Nijmegen, Toernooiveld 1, 6523 ED Nijmegen, The Netherlands. gijs.afink@cck.ki.se
Westermark
Ulrica K
UK
Lammerts
Ellen
E
Nistér
Monica
M
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015152:Blotting, Northern; D022762:CCAAT-Enhancer-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D017353:Gene Deletion; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010006:Osteoblasts / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012313:RNA / Q000737:chemistry; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000737:chemistry* / Q000378:metabolism; D012509:Sarcoma / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D014162:Transfection
D022762:CCAAT-Enhancer-Binding Proteins; D007375:Interleukin-1; D007378:Interleukins; D010982:Platelet-Derived Growth Factor; D012313:RNA; D008156:Luciferases; D020796:Receptor, Platelet-Derived Growth Factor alpha