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Production of Nurr-1 Specific Polyclonal Antibodies Free of Cross-reactivity Against Its Close Homologs, Nor1 and Nur77
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Production of Nurr-1 Specific Polyclonal Antibodies Free of Cross-reactivity Against Its Close Homologs, Nor1 and Nur77

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Transcriptional activation of known and novel apoptotic pathways by Nur77 orphan steroid receptor

Arvind Rajpal1, Yuri A Cho, Biana Yelent

  • 1Department of Molecular and Cell Biology, Division of Immunology and Cancer Research Laboratory, 469 LSA, University of California, Berkeley, CA 94720-3200, USA.

The EMBO Journal
|December 6, 2003
PubMed

Insights

Nur77 (nuclear orphan steroid receptor) triggers T cell apoptosis via gene activation, not mitochondrial pathways. This process involves novel genes NDG1/NDG2 and is independent of Bcl-2, revealing new insights into T cell survival regulation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Death Research

Background:

  • Nur77, a nuclear orphan steroid receptor, is linked to negative selection in thymocytes.
  • The precise mechanism of Nur77-induced apoptosis remains unclear, with some studies suggesting a transcription-independent mitochondrial pathway.
  • This pathway involves cytochrome c release, but its role in T cell apoptosis is debated.

Purpose of the Study:

  • To elucidate the mechanism of Nur77-mediated apoptosis in thymocytes.
  • To investigate whether Nur77-induced apoptosis involves cytoplasmic cytochrome c release or Bcl-2 rescue.
  • To identify novel genes and pathways regulated by Nur77 during apoptosis.

Main Methods:

  • Expression of Nur77 in thymocytes and cell lines.
  • Analysis of apoptosis and cytochrome c release.
  • Microarray analysis to identify Nur77-induced genes.
  • Characterization of novel genes NDG1 and NDG2.

Main Results:

  • Nur77-mediated apoptosis in thymocytes does not involve cytoplasmic cytochrome c release and is not rescued by Bcl-2.
  • Microarray analysis revealed Nur77 induces known apoptotic genes (FasL, TRAIL) and two novel genes (NDG1, NDG2).
  • NDG1 initiates a novel apoptotic pathway that is independent of Bcl-2.

Conclusions:

  • Nur77-mediated apoptosis in T cells is primarily driven by Bcl-2-independent transcriptional activation.
  • This process involves both known and novel apoptotic pathways, including those initiated by NDG1.
  • The findings clarify the mechanism of Nur77-induced apoptosis, highlighting its transcriptional basis and Bcl-2 independence in T cells.

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