Transcriptional activity of interferon regulatory factor (IRF)-3 depends on multiple protein-protein interactions.

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.
Mesh Terms:
Amino Acid Sequence, Animals, Blotting, Western, Cell Nucleus, DNA, DNA-Binding Proteins, Dimerization, E1A-Associated p300 Protein, Glutathione Transferase, Humans, Interferon Regulatory Factor-3, Mice, Molecular Sequence Data, Mutation, Nuclear Proteins, Phosphorylation, Plasmids, Protein Binding, Protein Biosynthesis, Protein Structure, Tertiary, Recombinant Fusion Proteins, Serine, Threonine, Trans-Activators, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection, Tumor Cells, Cultured
Eur. J. Biochem.
Date: Dec. 01, 2002
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