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J. Biol. Chem., Vol. 275, Issue 27, 20406-20411, July 7, 2000
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From the Department of Molecular Biology, Lerner Research
Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44145
The LMP2 gene, which encodes a protein required
for efficient presentation of viral antigens, requires both
unphosphorylated Stat1 and IRF1 for basal expression. LMP2 expression
is down-regulated by the adenovirus protein E1A, which binds to Stat1
and CBP/p300, and by the mutant E1A protein RG2, which binds to Stat1
but not to CBP/p300, but not by the mutant protein
Adenovirus E1A Down-regulates LMP2 Transcription by Interfering
with the Binding of Stat1 to IRF1*
2-36, which does
not bind to either Stat1 or CBP/p300. Stat1 and IRF1 associate in untreated cells and bind as a complex to the overlapping ICS-2/GAS element of the LMP2 promoter. E1A interferes with the formation of this
complex by occupying domains of Stat1 that bind to IRF1. These results
reveal how adenovirus infection attenuates LMP2 expression, thereby
interfering with the presentation of viral antigens.
*
This work was supported by a grant from Ares-Serono.The costs of publication of this
article were defrayed in part by the payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom all correspondence should be addressed: Dept. of Molecular
Biology, Lerner Research Inst., Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44145. E-mail: starkg@ccf.org.
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