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NF45/ILF2 tissue expression, promoter analysis, and interleukin-2 transactivating function.

Guohua Zhao1, Lingfang Shi, Daoming Qiu

  • 1Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305-5236, USA.

Experimental Cell Research
|April 9, 2005
PubMed
Summary
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Nuclear factor 45 (NF45) acts as a transcriptional activator, notably boosting interleukin-2 (IL-2) gene expression. This protein is conserved and regulated, with increased mRNA found in certain blood cancers.

Area of Science:

  • Molecular Biology
  • Immunology
  • Genetics

Background:

  • Nuclear factor 45 (NF45/ILF2) interacts with NF90/ILF3 in the nucleus.
  • NF45 regulates interleukin-2 (IL-2) gene transcription at the antigen receptor response element (ARRE)/NF-AT DNA target sequence.
  • NF45 is broadly expressed in normal tissues, with elevated mRNA levels in lymphoma and leukemia cell lines.

Purpose of the Study:

  • To characterize the function of human NF45 in regulating IL-2 gene expression.
  • To investigate the transcriptional activation role of NF45.

Main Methods:

  • Analysis of NF45 protein distribution and gene localization (chromosome 1q21.3 in humans, 3F1 in mice).
  • Murine NF45 gene promoter analysis, including CCAAT-box binding factors.
  • Functional characterization in Jurkat T-cells using sense and antisense NF45 cDNA transfections with IL-2 luciferase reporter assays.

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Main Results:

  • NF45 sense expression significantly increased IL-2 luciferase reporter gene activity (120-fold) and IL-2 protein expression (2-fold) in Jurkat T-cells.
  • NF45 gene promoter analysis indicated activation by factors binding to the CCAAT-box.
  • Human and murine NF45 proteins show high conservation, differing by only one amino acid.

Conclusions:

  • NF45 is a highly conserved and regulated transcriptional activator.
  • Interleukin-2 (IL-2) is a target gene regulated by NF45.
  • NF45 plays a significant role in IL-2 gene regulation.