An activation-defective mutant of the human cytomegalovirus IE2p86 protein inhibits NF-kappaB-mediated stimulation of the human interleukin-6 promoter.
The IE2p86 protein of human cytomegalovirus is an essential activator of early- and late-phase viral gene expression. Whilst IE2p86 activates expression of a number of cellular genes, it also represses certain cellular genes, particularly those activated by nuclear factor kappaB (NF-kappaB). As the interleukin-6 (IL-6) promoter can be activated by both NF-kappaB and IE2p86, it was examined whether there is competition between these two factors. Here, it is reported that both wild-type and mutant IE2p86 can block activation of the IL-6 promoter in response to interleukin-1beta. By using an artificial activator in which the activation domain of NF-kappaB is directed to the promoter by the GAL4 DNA-binding domain, it is shown that the mutant form of IE2p86 can inhibit NF-kappaB-mediated activation at a step subsequent to promoter recruitment. These data therefore suggest a novel mechanism for inhibition of NF-kappaB by IE2p86.
Gealy
Claire
C
Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, UK.
Humphreys
Christine
C
Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, UK.
Dickinson
Vicky
V
Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, UK.
Stinski
Mark
M
Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Caswell
Richard
R
Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, UK.
D045744:Cell Line, Tumor; D003587:Cytomegalovirus / Q000235:genetics*; D005786:Gene Expression Regulation / Q000276:immunology; D015967:Gene Expression Regulation, Viral; D005909:Glioblastoma; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000235:genetics* / Q000494:pharmacology*; D014162:Transfection
C069186:IE2 protein, Cytomegalovirus; D017874:Immediate-Early Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D015534:Trans-Activators