| First Author | Pan J | Year | 1998 |
| Journal | J Biol Chem | Volume | 273 |
| Issue | 16 | Pages | 10068-77 |
| PubMed ID | 9545354 | Mgi Jnum | J:47038 |
| Mgi Id | MGI:1202519 | Doi | 10.1074/jbc.273.16.10068 |
| Citation | Pan J, et al. (1998) Tumor necrosis factor-alpha- or lipopolysaccharide-induced expression of the murine P-selectin gene in endothelial cells involves novel kappaB sites and a variant activating transcription factor/ cAMP response element. J Biol Chem 273(16):10068-77 |
| abstractText | Tumor necrosis factor-alpha (TNF-alpha) or lipopolysaccharide (LPS) increases expression of the P-selectin gene in murine, but not in human, endothelial cells. These mediators augment expression of a reporter gene driven by the murine, but not the human, P-selectin promoter in transfected endothelial cells. The regions from -593 to - 474 and from -229 to -13 in the murine P-selectin promoter are required for TNF-alpha or LPS to stimulate reporter gene expression. Within these regions, we identified two tandem kappaB elements, a reverse-oriented kappaB site and a variant activating transcription factor/cAMP response element (ATF/CRE), that participate in TNF-alpha- or LPS-induced expression. The tandem kappaB elements bound to NF-kappaB heterodimers and p65 homodimers, the reverse-oriented kappaB site bound to p65 homodimers, and the variant ATF/CRE bound to nuclear proteins that included activating transcription factor-2. Mutations in each individual element eliminated binding to nuclear proteins and decreased by 20-60% the TNF-alpha- or LPS-induced expression of a reporter gene driven by the murine P-selectin promoter in transfected endothelial cells. Simultaneous mutations of all elements further decreased, but did not abolish, induced expression. Co-overexpression of p50 and p65 enhanced murine P-selectin promoter activity in a kappaB site-dependent manner. These data indicate that the kappaB sites and the variant ATF/CRE are required for TNF-alpha or LPS to optimally induce expression of the murine P-selectin gene. The presence of these elements in the murine, but not the human, P-selectin gene may explain in part why TNF-alpha or LPS stimulates transcription of P-selectin in a species-specific manner. |
