Tumor necrosis factor-alpha activation by adenovirus E1A 13S CR3 occurs in a cell-dependent and cell-independent manner.

摘要

The adenovirus (Ad) early gene product 13S transactivates the tumor necrosis factor (TNF)-alpha promoter in inflammatory cells. We examined both the subdomains of E1A and the upstream TNF promoter elements involved. In both Jurkat and U-937 cells, zinc finger or carboxyl region mutation of Ad E1A 13S conserved region 3 resulted in a significant loss of transactivation of the TNF promoter (> or =69%). For both cell types there was a TNF-negative regulatory element in the -242 to -199 region and a positive regulatory element between -199 and -118. In contrast, an upstream positive regulatory element was detected in different regions in both cell types. In U-937 cells the positive regulatory unit was between -600 and -576, whereas in Jurkat cells it was between -576 and -242. The U-937 upstream element was dependent on a site previously designated epsilon in cooperation with an adjacent nuclear factor-kappaB-2a site. Therefore, transactivation of the TNF promoter by Ad 13S in lymphocyte and monocyte cell types involves similar subdomains of the E1A protein, but cell-specific TNF promoter elements.