Overexpression of c-Fos enhances the transcription of human arachidonate 12-lipoxygenase in A431 cells.
The effect of transient transfection with expression vector of c-Fos on the expression of 12-lipoxygenase in human epidermoid carcinoma A431 cells was studied. Overexpression of c-Fos increased the expression of 12-lipoxygenase mRNA and enzyme activity, and also activated the promoter activity of 12-lipoxygenase gene in a dose-dependent manner. Co-transfection with c-Fos and c-Jun expression vectors in cells synergistically increased the promoter activity of 12-lipoxygenase. With the aid of additional 5'-deletion and site-directed mutagenesis, the downstream and middle Sp1 sites residing at -123 to -114 bp and -158 to -150 bp were found to be critical for the c-Fos response of activating the transcription of human 12-lipoxygenase gene. Furthermore, the specific role of Sp1 in c-Fos response was confirmed by using the reporter plasmid driven by SV40 early promoter. These results indicate that the requirement of Sp1-binding sites in the promoter region of 12-lipoxygenase gene for c-Fos response is similar to that previously observed in EGF response.
Chen
B K
BK
College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan.
Chang
W C
WC
D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D016384:Consensus Sequence; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D016762:Genes, fos / Q000235:genetics*; D016758:Genes, jun / Q000235:genetics; D006801:Humans; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D004247:DNA; D001092:Arachidonate 12-Lipoxygenase