Abstract
Nur77 is a transcription factor that is induced to a high level during TCR-mediated apoptosis of thymocytes and T cell hybridomas. Expression of a dominant-negative mutant of Nur77 can inhibit TCR-mediated apoptosis, while constitutive expression of full-length Nur77 in thymocytes leads to massive apoptosis. Nur77 is similar to the steroid receptor family and consists of a transactivation, a DNA-binding and a C-terminal 'ligand-binding' domain. In contrast to the other nuclear receptors, Nur77 activity does not appear to depend on any ligand. However, its C-terminal region can regulate its transactivation activity. A short C-terminal deletion results in a protein with only 15-20% activity while deletion of the entire C-terminal region increases its activity. To further study the role of Nur77 transcription in apoptosis, we have generated transgenic mice expressing Nur77 with a short C-terminal deletion or Nur77 without its entire C-terminal domain. Mice expressing the shorter deletion/transcriptionally less active mutant displayed a mild phenotype. However, mice with the larger deletion/more transcriptionally active mutant showed massive thymocyte apoptosis. These data suggest that Nur77 transcription correlates with its apoptotic function in vivo.
Original language | English (US) |
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Pages (from-to) | 3722-3728 |
Number of pages | 7 |
Journal | European Journal of Immunology |
Volume | 29 |
Issue number | 11 |
DOIs | |
State | Published - 1999 |
Externally published | Yes |
Keywords
- Apoptosis
- NGFI-B
- Steroid nuclear receptor
- Transcription factor
- Transgenic mouse
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology