Nur77 transcription activity correlates with its apoptotic function in vivo

Anna A. Kuang, Dragana Cado, Astar Winoto

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    56 Scopus citations

    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 - Nov 22 1999

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    Keywords

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

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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