Nur77 transcription activity correlates with its apoptotic function in vivo

Anna Kuang, Dragana Cado, Astar Winoto

Research output: Contribution to journalArticle

56 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)3722-3728
Number of pages7
JournalEuropean Journal of Immunology
Volume29
Issue number11
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Apoptosis
Thymocytes
Transcriptional Activation
Ligands
Steroid Receptors
Hybridomas
Cytoplasmic and Nuclear Receptors
Transgenic Mice
Transcription Factors
T-Lymphocytes
Phenotype
DNA
Proteins

Keywords

  • Apoptosis
  • NGFI-B
  • Steroid nuclear receptor
  • Transcription factor
  • Transgenic mouse

ASJC Scopus subject areas

  • Immunology

Cite this

Nur77 transcription activity correlates with its apoptotic function in vivo. / Kuang, Anna; Cado, Dragana; Winoto, Astar.

In: European Journal of Immunology, Vol. 29, No. 11, 1999, p. 3722-3728.

Research output: Contribution to journalArticle

Kuang, Anna ; Cado, Dragana ; Winoto, Astar. / Nur77 transcription activity correlates with its apoptotic function in vivo. In: European Journal of Immunology. 1999 ; Vol. 29, No. 11. pp. 3722-3728.
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