Tumor necrosis factor-alpha activation by adenovirus E1A 13S CR3 occurs in a cell-dependent and cell-independent manner.
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.
Sanchez
Traci A
TA
Department of Internal Medicine, Pulmonary and Critical Care Division, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA.
Booth
J Leland
JL
Metcalf
Jordan P
JP
D017500:Adenovirus E1A Proteins / Q000494:pharmacology; D001483:Base Sequence / Q000235:genetics; D002460:Cell Line; D002468:Cell Physiological Phenomena; D017124:Conserved Sequence; D017353:Gene Deletion; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000502:physiology*; D012045:Regulatory Sequences, Nucleic Acid / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
D017500:Adenovirus E1A Proteins; D014409:Tumor Necrosis Factor-alpha