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Modulation of cytokine‐induced HIV gene expression by competitive binding of transcription factors to the coactivator p300
Author(s) -
Hottiger Michael O.,
Felzien Lisa K.,
Nabel Gary J.
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.11.3124
Subject(s) - stat2 , biology , coactivator , stat1 , transcription factor , stat protein , taf2 , response element , transcription (linguistics) , gene expression , microbiology and biotechnology , tcf4 , stat6 , signal transduction , cancer research , promoter , gene , enhancer , genetics , stat3 , linguistics , philosophy
The host response to viral infection involves the secretion of multiple cytokines which alter immune function and viral replication. These proteins activate several signal transduction pathways in infected cells which must be integrated to regulate cellular and viral gene expression. In this report, we demonstrate that specific transcription factors induced by distinct cytokines regulate HIV transcription by competitive binding to the p300 coactivator. Interferon‐α (IFN‐α) was found to inhibit NF‐κB‐dependent HIV gene expression stimulated by tumor necrosis factor‐α (TNF‐α). This inhibition was mediated by binding of the IFN‐α signal transducer and activator of transcription 2, Stat2, to a specific domain of p300 which also binds to the RelA (p65) subunit of NF‐κB. p300 was found to be limiting with respect to RelA (p65) and Stat2, and this effect was reversed by overexpression of p300. Inhibition by Stat2 was specific for NF‐κB and was not mediated by Stat1, which is also induced by IFN‐α. Gene activation induced by the Stat2 transcription domain was also inhibited by expression of RelA. These results demonstrate that HIV transcription can be regulated in the nucleus by competitive binding of specific cytokine‐induced transcription factors to a discrete domain of a transcriptional coactivator.