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.
Nature Publishing Group
344 - 347
Adenoviridae/ph [Physiology] Adenovirus E1A Proteins/me [Metabolism] Binding Sites DNA-Binding Proteins/ai [Antagonists & Inhibitors] DNA-Binding Proteins/ge [Genetics] *DNA-Binding Proteins/me [Metabolism] Gene Expression Regulation Hela Cells Human *Interferon-alpha/ph [Physiology] *Nuclear Proteins/me [Metabolism] Protein Binding *Signal Transduction Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Trans-Activators/ai [Antagonists & Inhibitors] *Trans-Activators/me [Metabolism] Transcription Factors/ai [Antagonists & Inhibitors] Transcription Factors/ge [Genetics] *Transcription Factors/me [Metabolism] Tumor Cells, Cultured Virus Replication