A non-classical ISRE/ISGF3 pathway mediates induction of RANTES gene transcription by type I IFNs

FEBS Lett. 2002 Jan 30;511(1-3):41-5. doi: 10.1016/s0014-5793(01)03276-8.

Abstract

RANTES (regulated upon activation normal T cell expressed and secreted) is a chemoattractant cytokine important in the generation of inflammatory responses and human immunodeficiency virus resistance. In hematopoietic cells, RANTES is over-expressed by type I interferons (IFN-alpha and IFN-beta). The upstream region of the RANTES gene promoter contains a distal low affinity IFN-stimulated response element (ISRE). Specific mutagenesis in this ISRE-like motif abolished the activation of RANTES transcription by type I IFNs. Examination of the ISRE binding factors strongly suggested that signal transducer and activator of transcription (Stat)-2 and p48/IFN-stimulated gene factor 3gamma (ISGF3gamma) are not required for the induction of RANTES by type I IFNs. The specific requirement of Stat-1 was demonstrated using Stat-1-deficient U3A cells. These results revealed a non-classical ISRE/ISGF3 signal transduction pathway for the induction of RANTES by type I IFNs.

MeSH terms

  • Base Sequence
  • Cell Line
  • Chemokine CCL5 / genetics*
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Humans
  • Interferon Type I / pharmacology*
  • Interferon-Stimulated Gene Factor 3
  • Interferon-Stimulated Gene Factor 3, gamma Subunit
  • Jurkat Cells
  • Molecular Sequence Data
  • Mutation / genetics
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Response Elements / genetics*
  • STAT1 Transcription Factor
  • STAT2 Transcription Factor
  • Signal Transduction / drug effects*
  • Trans-Activators / deficiency
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism*
  • Transcription, Genetic / drug effects*
  • Up-Regulation / drug effects*

Substances

  • Chemokine CCL5
  • DNA-Binding Proteins
  • IRF9 protein, human
  • Interferon Type I
  • Interferon-Stimulated Gene Factor 3
  • Interferon-Stimulated Gene Factor 3, gamma Subunit
  • RNA, Messenger
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT2 Transcription Factor
  • STAT2 protein, human
  • Trans-Activators
  • Transcription Factors
  • DNA