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Molecular characterization of the Nur77 orphan steroid receptor in apoptosis
1Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200.
Abstract:
One of the in vitro model of programmed cell death is T cell receptor (TCR)-mediated apoptosis of immature T cells and T cell hybridomas. This form of apoptosis requires newly gene synthesis and may relate to negative selection during T cell development. Recently, an orphan steroid receptor Nur77 was found to be induced during TCR-mediated apoptosis. When introduced into T cells, a dominant negative or antisense Nur77 construct can block the apoptosis process. Various inhibitors of TCR-mediated apoptosis, including cyclosporin A down-regulate the Nur77 DNA binding activity. Thus, the Nur77 protein family may play a crucial role during T cell apoptosis.
Insights
Nur77, a steroid receptor, is induced during T cell receptor (TCR)-mediated apoptosis. Blocking Nur77 inhibits this programmed cell death, suggesting its crucial role in T cell development and apoptosis.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- T cell receptor (TCR)-mediated apoptosis is a key in vitro model for programmed cell death.
- This process involves new gene synthesis and is implicated in T cell development's negative selection.
Purpose of the Study:
- To investigate the role of the orphan steroid receptor Nur77 in TCR-mediated apoptosis.
- To determine if Nur77 is involved in the regulation of T cell apoptosis.
Main Methods:
- Studying TCR-mediated apoptosis in T cells and T cell hybridomas.
- Introducing dominant negative or antisense Nur77 constructs into T cells.
- Analyzing the effect of apoptosis inhibitors like cyclosporin A on Nur77 DNA binding activity.
Main Results:
- Nur77 expression is induced during TCR-mediated apoptosis.
- Inhibition of Nur77 function blocks the apoptosis process.
- Cyclosporin A, an apoptosis inhibitor, down-regulates Nur77 DNA binding activity.
Conclusions:
- The Nur77 protein family plays a critical role in regulating T cell apoptosis.
- Nur77 is a key mediator of TCR-induced programmed cell death in T cells.