Interferon regulatory factor-7 synergizes with other transcription factors through multiple interactions with p300/CBP coactivators

J Biol Chem. 2003 May 2;278(18):15495-504. doi: 10.1074/jbc.M212940200. Epub 2003 Feb 25.

Abstract

Interferon regulatory factor (IRF)-7 is activated in response to virus infection and stimulates the transcription of a set of cellular genes involved in host antiviral defense. The mechanism by which IRF-7 is activated and cooperates with other transcription factors is not fully elucidated. Activation of IRF-7 results from a conformational change triggered by the virus-dependent phosphorylation of its C terminus. This conformational change leads to dimerization, nuclear accumulation, DNA-binding, and transcriptional transactivation. Here we show that activation of IRF-7, like that of IRF-3, is dependent on modifications of two distinct sets of Ser/Thr residues. Moreover, we show that different virus-inducible cis-acting elements display requirements for specific IRFs. In particular, the virus-responsive element of the ISG15 gene promoter can be activated by either IRF-3 or IRF-7 alone, whereas the P31 element of the interferon-beta gene is robustly activated only when IRF-3, IRF-7, and the p300/CBP coactivators are all present. Furthermore, we find that IRF-7 interacts with four distinct regions of p300/CBP. These interactions not only stimulate the intrinsic transcriptional activity of IRF-7, but they are also indispensable for its ability to strongly synergize with other transcription factors, including c-Jun and IRF-3.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / physiology*
  • Humans
  • Interferon Regulatory Factor-3
  • Interferon Regulatory Factor-7
  • Molecular Sequence Data
  • Nuclear Proteins / physiology*
  • Protein Conformation
  • Proto-Oncogene Proteins c-jun / physiology
  • Rabbits
  • Structure-Activity Relationship
  • Trans-Activators / physiology*
  • Transcription Factors / physiology*
  • Transcriptional Activation
  • Virus Activation

Substances

  • DNA-Binding Proteins
  • IRF3 protein, human
  • IRF7 protein, human
  • Interferon Regulatory Factor-3
  • Interferon Regulatory Factor-7
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-jun
  • Trans-Activators
  • Transcription Factors
  • DNA