iii) E1A
repression of IL-6-induced gene activation by blocking the assembly
of IL-6 response element binding complexes. Takeda-T; Nakajima-K;
Kojima-H; Hirano-T, J-Immunol. 1994 Nov 15; 153(10): 4573-82iii) E1A
repression of IL-6-induced gene activation by blocking the assembly
of IL-6 response element binding complexes. Takeda-T; Nakajima-K;
Kojima-H; Hirano-T, J-Immunol. 1994 Nov 15; 153(10): 4573-82
Some viral products interfere with host antiviral defense mechanisms.
Adenovirus E1A represses IFN signal transduction pathways which
induces gene activation and an antiviral state. Both IFN and IL-6
activate Jak/Tyk protein tyrosine kinases and the STAT (signal
transducer and activator of transcription) family proteins. We showed
that 12S E1A repressed IL-6 signals activating the junB promoter and
the two IL-6 response elements (REs), JRE-IL6 and type II IL-6 RE
(also called acute phase response element), required for IL-6-induced
activation of the junB promoter and the type II acute phase reactant
genes, respectively, in hepatocytes. Conserved region 1 of the 12S
E1A was responsible for the repression. Target molecules of the
repression by E1A appeared to be IL-6-inducible DNA-binding proteins
acting on the IL-6 REs. In a rat 3Y1 cell line stably expressing E1A,
the levels of IL-6-induced IL-6 RE binding proteins were severely
reduced compared with those in a parental 3Y1 cell line. Moreover, we
found that the levels of the STAT family proteins including
Stat1-alpha (p91), Stat1-beta (p84), Stat2 (p113), and Stat3 were
decreased by the stable expression of adenovirus E1A. The E1A-induced
reduction in the amount of DNA-binding proteins seemed to be partly
responsible for the decreased transcriptional activity of the IL-6
RE-driven gene expression in response to IL-6. This repression
mechanism may be applicable to the E1A repression of
IFN-gamma-induced gene activation.
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