Journal
EUROPEAN JOURNAL OF BIOCHEMISTRY
Volume 269, Issue 24, Pages 6142-6151Publisher
BLACKWELL PUBLISHING LTD
DOI: 10.1046/j.1432-1033.2002.03330.x
Keywords
interferon; IRF-3; coactivator; virus; transcription
Categories
Funding
- NIAID NIH HHS [AI20642] Funding Source: Medline
Ask authors/readers for more resources
Virus infection results in the activation of a set of cellular genes involved in host antiviral defense. IRF-3 has been identified as a critical transcription factor in this process. The activation mechanism of IRF-3 is not fully elucidated, yet it involves a conformational change triggered by the virus-dependent phosphorylation of its C-terminus. This conformational change leads to nuclear accumulation, DNA binding and transcriptional transactivation. Here we show that two distinct sets of Ser/Thr residues of IRF-3, on phosphorylation, synergize functionally to achieve maximal activation. Remarkably, we find that activated IRF-3 lacks transcriptional activity, but activates transcription entirely through the recruitment of the p300/CBP coactivators. Moreover, we show that two separate domains of IRF-3 interact with several distinct regions of p300/CBP. Interference with any of these interactions leads to a complete loss of transcriptional activity, suggesting that a bivalent interaction is essential for coactivator recruitment by IRF-3.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available