Abstract
We have identified a virus-activated factor (VAF) that binds to a regulatory element shared by different virus-inducible genes. We provide evidence that VAF contains two members of the interferon regulatory factor (IRF) family of transcriptional activator proteins (IRF-3 and IRF-7), as well as the transcriptional coactivator proteins p300 and CBP. Remarkably, VAF, as well as recombinant IRF-3 and IRF-7 proteins, binds very weakly to the interferon-beta (IFN-beta) gene promoter in vitro. However, in virus-infected cells, both proteins are recruited to the endogenous IFN-beta promoter as part of a protein complex that includes ATF-2/c-Jun and NF-kappa B. These observations provide a unique example of the coordinate activation of multiple transcriptional activator proteins and their highly cooperative assembly into a transcriptional enhancer complex in vivo.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Activating Transcription Factor 2
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Animals
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Base Sequence
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CHO Cells
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CREB-Binding Protein
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Cell Nucleus / chemistry
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Cell Nucleus / metabolism
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Cell Nucleus / virology
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Cricetinae
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Cyclic AMP Response Element-Binding Protein / metabolism
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DNA / metabolism
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DNA-Binding Proteins / metabolism
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Enhancer Elements, Genetic / physiology*
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Fungal Proteins / genetics
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Gene Expression Regulation, Viral
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HeLa Cells
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Humans
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Interferon Regulatory Factor-3
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Interferon Regulatory Factor-7
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Interferon-beta / genetics*
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Interferon-beta / metabolism
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Leucine Zippers / physiology
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Molecular Sequence Data
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NF-kappa B / metabolism
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Nuclear Proteins / analysis
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Phosphorylation
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Recombinant Fusion Proteins / metabolism
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Respirovirus / genetics*
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Respirovirus / metabolism
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Respirovirus Infections / genetics*
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Respirovirus Infections / metabolism
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Saccharomyces cerevisiae Proteins*
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Trans-Activators*
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Transcription Factors / analysis
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription, Genetic / physiology*
Substances
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ATF2 protein, human
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Activating Transcription Factor 2
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Cyclic AMP Response Element-Binding Protein
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DNA-Binding Proteins
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Fungal Proteins
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GAL4 protein, S cerevisiae
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IRF3 protein, human
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IRF7 protein, human
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Interferon Regulatory Factor-3
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Interferon Regulatory Factor-7
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NF-kappa B
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Nuclear Proteins
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Recombinant Fusion Proteins
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Saccharomyces cerevisiae Proteins
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Trans-Activators
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Transcription Factors
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Interferon-beta
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DNA
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CREB-Binding Protein
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CREBBP protein, human