Functional redundancy of the Nur77 and Nor-1 orphan steroid receptors in T-cell apoptosis
Open Access
- 15 April 1997
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 16 (8), 1865-1875
- https://doi.org/10.1093/emboj/16.8.1865
Abstract
The transcription factor Nur77 (NGFI‐B), a member of the steroid nuclear receptor superfamily, is induced to a high level during T‐cell receptor (TCR)‐mediated apoptosis. A transgenic dominant‐negative Nur77 protein can inhibit the apoptotic process accompanying negative selection in thymocytes, while constitutive expression of Nur77 leads to massive cell death. Nur77‐deficient mice, however, have no phenotype, suggesting the possible existence of a protein with redundant function to Nur77. To explore this possibility, we have characterized the role of two Nur77 family members, Nurr1 and Nor‐1, in TCR‐induced apoptosis. We found that Nor‐1 and Nurr1 can transactivate through the same DNA element as Nur77, and that their transactivation activities can be blocked by a Nur77 dominant‐negative protein. In thymocytes, Nor‐1 protein is induced to a very high level upon TCR stimulation and has similar kinetics to Nur77. In contrast, Nurr1 is undetectable in stimulated thymocytes. Furthermore, constitutive expression of Nor‐1 in thymocytes leads to massive apoptosis and up‐regulation of CD25, suggesting a functional redundancy between Nur77 and Nor‐1 gene products. As in the case of our Nur77‐FL mice, FasL is not detectable in the thymocytes of Nor‐1 transgenic mice. Constitutive expression of Nur77 in gld/gld mice rescues the lymphoproliferative phenotype of the FasL mutant mice. Thus, Nor‐1 and Nur77 demonstrate functional redundancy in an apparently Fas‐independent apoptosis.Keywords
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