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Interferon regulatory factor 2 binding protein 2 is a new NFAT1 partner and represses its transcriptional activity

Flávia R G Carneiro1, Renata Ramalho-Oliveira, Giuliana P Mognol

  • 1Division of Cellular Biology, Brazilian National Cancer Institute, Rio de Janeiro, Brazil.

Molecular and Cellular Biology
|May 18, 2011
PubMed

Insights

Interferon regulatory factor 2 binding protein 2 (IRF-2BP2) acts as a transcriptional repressor, specifically inhibiting the NFAT1 transcription factor. This interaction reduces the production of key immune signaling molecules like IL-2 and IL-4.

Area of Science:

  • Molecular Biology
  • Immunology
  • Transcription Regulation

Background:

  • Nuclear factor of activated T cells (NFAT) proteins are crucial transcription factors regulating cell cycle, differentiation, and apoptosis.
  • NFAT proteins possess conserved DNA-binding and regulatory domains, but their N- and C-terminal transactivation sites have poorly understood functions.

Purpose of the Study:

  • To identify novel regulators of NFAT1 activity.
  • To elucidate the molecular mechanism by which IRF-2BP2 interacts with and modulates NFAT1 function.

Main Methods:

  • Interaction studies to identify proteins binding to NFAT1's C-terminal domain.
  • Gene reporter assays to assess the impact of IRF-2BP2 on NFAT1-driven transcription.
  • Ectopic expression of IRF-2BP2 in CD4 T cells to evaluate its effect on cytokine production.
  • Subcellular localization studies of IRF-2BP2 and its functional mutants.

Main Results:

  • Interferon regulatory factor 2 binding protein 2 (IRF-2BP2) was identified as a specific interactor of the NFAT1 C-terminal domain.
  • IRF-2BP2 functions as a transcriptional repressor, inhibiting NFAT1-dependent transactivation of target gene promoters.
  • Ectopic IRF-2BP2 expression in CD4 T cells led to decreased production of interleukin-2 (IL-2) and IL-4.
  • NFAT1 and IRF-2BP2 colocalize in the nucleus of activated cells; nuclear localization of IRF-2BP2 is essential for its repressive activity.

Conclusions:

  • IRF-2BP2 is a novel negative regulator of the NFAT1 transcription factor.
  • IRF-2BP2 mediates transcriptional repression of NFAT1 activity, impacting immune cell function.
  • The nuclear localization of IRF-2BP2 is critical for its role in repressing NFAT1.

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