Abstract
The transcription factor ISGF3 transduces interferon (IFN)-alpha signals and activates the transcription of cellular antiviral defence genes. Adenovirus E1A blocks the IFN-alpha response, allowing unhindered viral replication. ISGF3 consists of Stat1, Stat2 and p48. Here we show that p300 and/or CBP (CREB-binding protein), which are transcription adaptors targeted by E1A, interact specifically with Stat2. Binding occurs between the first cysteine-histidine-rich region of p300/CBP and the carboxy-terminal segment of Stat2, a domain essential for ISGF3 function. We find that this domain of Stat2 has transactivation potential, which correlates with its binding to p300/CBP. Moreover, E1A represses Stat2 transactivation and IFN-alpha-activated transcription by inhibiting p300/CBP function. This provides a new mechanism for inhibition of the IFN-alpha-activated antiviral response by E1A, and supports the view that E1A binding to p300/CBP has functional significance for adenovirus replication in its natural host.
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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Adenoviridae / physiology
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Adenovirus E1A Proteins / metabolism
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Binding Sites
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CREB-Binding Protein
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation
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HeLa Cells
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Humans
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Interferon-Stimulated Gene Factor 3
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Interferon-Stimulated Gene Factor 3, gamma Subunit
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Interferon-alpha / physiology*
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Nuclear Proteins / metabolism*
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Protein Binding
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STAT2 Transcription Factor
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Signal Transduction*
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Trans-Activators / antagonists & inhibitors
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Trans-Activators / metabolism*
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Tumor Cells, Cultured
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Virus Replication
Substances
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Adenovirus E1A Proteins
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DNA-Binding Proteins
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IRF9 protein, human
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Interferon-Stimulated Gene Factor 3
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Interferon-Stimulated Gene Factor 3, gamma Subunit
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Interferon-alpha
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Nuclear Proteins
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STAT2 Transcription Factor
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STAT2 protein, human
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Trans-Activators
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Transcription Factors
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CREB-Binding Protein
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CREBBP protein, human