Cooperation of Stat2 and p300/CBP in signalling induced by interferon-alpha

THE transcription factor ISGF3 transduces interferon (IFN)-alpha signals and activates the transcription of cellular antiviral defence genes(1,2). Adenovirus EIA blocks the IFN-alpha response, allowing unhindered viral replication(3-5). 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(6). 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 ELA, and supports the view that E1A binding to p300/CBP has functional significance for adenovirus replication in its natural host.