Nur77 transcription activity correlates with its apoptotic function in vivo

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 dom inant-negative mutant of Nur77 can inhibit TCR-mediated apoptosis, while co nstitutive expression of full-length Nur77 in thymocytes leads to massive a poptosis. Nur77 is similar to the steroid receptor family and consists of a transactivation, a DNA-binding and a C-terminal "ligand-binding" domain. I n contrast to the other nuclear receptors, Nur77 activity does not appear t o depend on any ligand. However, its C-terminal region can regulate its tra nsactivation activity. A short C-terminal deletion results in a protein wit h only 15-20 % activity while deletion of the entire C-terminal region incr eases its activity. To further study the role of Nur77 transcription in apo ptosis, we have generated transgenic mice expressing Nur77 with a short C-t erminal deletion or Nur77 without its entire C-terminal domain. Mice expres sing the shorter deletion/transcriptionally less active mutant displayed a mild phenotype. However, mice with the larger deletion/more transcriptional ly active mutant showed massive thymocyte apoptosis. These data suggest tha t Nur77 transcription correlates with its apoptotic function in vivo.