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 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.
Kuang
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Department of Molecular Biology, Division of Immunology and Cancer Research Laboratory, 469 LSA, University of California at Berkeley, Berkeley, USA.
Cado
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Winoto
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D000818:Animals; D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010641:Phenotype; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D019076:Transgenes
D004268:DNA-Binding Proteins; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors