Cooperation of Stat2 and p300/CBP in Signalling Induced by Interferon-Alpha

Nature. 1996 Sep 26;383(6598):344-7. doi: 10.1038/383344a0.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / physiology
  • Adenovirus E1A Proteins / metabolism
  • Binding Sites
  • CREB-Binding Protein
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Interferon-Stimulated Gene Factor 3
  • Interferon-Stimulated Gene Factor 3, gamma Subunit
  • Interferon-alpha / physiology*
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • STAT2 Transcription Factor
  • Signal Transduction*
  • Trans-Activators / antagonists & inhibitors
  • Trans-Activators / metabolism*
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured
  • Virus Replication

Substances

  • Adenovirus E1A Proteins
  • DNA-Binding Proteins
  • IRF9 protein, human
  • Interferon-Stimulated Gene Factor 3
  • Interferon-Stimulated Gene Factor 3, gamma Subunit
  • Interferon-alpha
  • Nuclear Proteins
  • STAT2 Transcription Factor
  • STAT2 protein, human
  • Trans-Activators
  • Transcription Factors
  • CREB-Binding Protein
  • CREBBP protein, human