Nur77 transcription activity correlates with its apoptotic function in vivo

Eur J Immunol. 1999 Nov;29(11):3722-8. doi: 10.1002/(SICI)1521-4141(199911)29:11<3722::AID-IMMU3722>3.0.CO;2-N.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Phenotype
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Sequence Deletion
  • T-Lymphocytes / cytology
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcription, Genetic
  • Transgenes


  • DNA-Binding Proteins
  • Nr4a1 protein, mouse
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Transcription Factors