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A novel interferon regulatory factor family transcription factor, ICSAT/Pip/LSIRF, that negatively regulates the

T Yamagata1, J Nishida, S Tanaka

  • 1Third Department of Internal Medicine, Tokyo University, Japan.

Molecular and Cellular Biology
|April 1, 1996
PubMed

Insights

We identified a new protein, interferon consensus sequence-binding protein (ICSAT), that regulates gene expression. ICSAT acts as a repressor, suggesting a novel "differential repression" mechanism in interferon-responsive genes.

Area of Science:

  • Immunology
  • Molecular Biology
  • Gene Regulation

Background:

  • Interferon (IFN) consensus sequences (ICSs) are crucial regulatory elements in IFN-responsive genes.
  • The Interferon Regulatory Factor (IRF) family plays a key role in mediating cellular responses to interferons.
  • Understanding novel regulators of IFN signaling is critical for comprehending immune responses and disease pathogenesis.

Purpose of the Study:

  • To isolate and characterize a novel cDNA clone encoding an IFN consensus sequence-binding protein (ICSAT).
  • To investigate the expression patterns and binding affinities of ICSAT.
  • To elucidate the functional role of ICSAT in regulating IFN-responsive gene expression.

Main Methods:

  • Isolation of a novel cDNA clone encoding ICSAT from adult T-cell leukemia and activated T cells.
  • Analysis of ICSAT expression in various T-cell lines, including HTLV-1 infected cells.
  • Binding affinity studies of ICSAT to different ICSs.
  • Cotransfection experiments using the N-Tera2 cell line to assess the functional role of ICSAT.

Main Results:

  • ICSAT was identified as the human homolog of Pip/LSIRF and is structurally related to ICSBP.
  • ICSAT expression is induced by HTLV-1 tax gene or PMA-A23187 stimulation in Jurkat cells.
  • ICSAT exhibits a repressive function on gene activation induced by IFN or IRF-1.
  • ICSAT demonstrates differential repression compared to IRF-2 and ICSBP on certain IFN-responsive reporter constructs.

Conclusions:

  • A novel protein, ICSAT, has been identified with a role in regulating IFN-responsive genes.
  • ICSAT functions as a repressor, contributing to a "differential repression" mechanism.
  • This mechanism involves multiple repressor proteins with distinct repressive effects, adding complexity to IFN-mediated gene regulation.

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