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A role for the orphan steroid receptor Nur77 in apoptosis accompanying antigen-induced negative selection.
The transcription factor Nur77, an orphan member of the nuclear hormone receptor superfamily, is highly expressed during T cell receptor-signaled apoptosis, suggesting a possible role for Nur77 in negative selection. We examined this by generating two sets of transgenic mice. In one set of mice, a dominant-negative Nur77 mutant is constitutively expressed and the other in which wild-type Nur77 protein is constitutively expressed in developing thymocytes. We report that inhibition of endogenous Nur77 by the dominant-negative mutant perturbed T cell development and inhibited antigen-induced negative selection in F5T cell receptor transgenic mice. Constitutive expression of wild-type Nur77 protein induced apoptosis in developing thymocytes, resulting in a decreased number of thymocytes and mature T cells. Together, these data support a role for Nur77 in the downstream signaling events in antigen-induced negative selection.
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Related Subject Headings
- Transcription Factors
- T-Lymphocytes
- Superantigens
- Receptors, Steroid
- Receptors, Cytoplasmic and Nuclear
- Nuclear Receptor Subfamily 4, Group A, Member 1
- Molecular Sequence Data
- Mice, Transgenic
- Mice, Inbred CBA
- Mice, Inbred C57BL
Citation
![Journal cover image](https://secure.syndetics.com/index.aspx?isbn=/lc.gif&issn=1097-4180&client=dukeuniv)
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Transcription Factors
- T-Lymphocytes
- Superantigens
- Receptors, Steroid
- Receptors, Cytoplasmic and Nuclear
- Nuclear Receptor Subfamily 4, Group A, Member 1
- Molecular Sequence Data
- Mice, Transgenic
- Mice, Inbred CBA
- Mice, Inbred C57BL