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Functional redundancy of the Nur77 and Nor-1 orphan steroid receptors in T-cell apoptosis.

Publication ,  Journal Article
Cheng, LE; Chan, FK; Cado, D; Winoto, A
Published in: EMBO J
April 15, 1997

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.

Duke Scholars

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Published In

EMBO J

DOI

ISSN

0261-4189

Publication Date

April 15, 1997

Volume

16

Issue

8

Start / End Page

1865 / 1875

Location

England

Related Subject Headings

  • Transcriptional Activation
  • Transcription Factors
  • Thymus Gland
  • T-Lymphocytes
  • Spleen
  • Receptors, Thyroid Hormone
  • Receptors, Steroid
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Antigen, T-Cell
  • Protein Binding
 

Citation

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Cheng, L. E., Chan, F. K., Cado, D., & Winoto, A. (1997). Functional redundancy of the Nur77 and Nor-1 orphan steroid receptors in T-cell apoptosis. EMBO J, 16(8), 1865–1875. https://doi.org/10.1093/emboj/16.8.1865
Cheng, L. E., F. K. Chan, D. Cado, and A. Winoto. “Functional redundancy of the Nur77 and Nor-1 orphan steroid receptors in T-cell apoptosis.EMBO J 16, no. 8 (April 15, 1997): 1865–75. https://doi.org/10.1093/emboj/16.8.1865.
Cheng LE, Chan FK, Cado D, Winoto A. Functional redundancy of the Nur77 and Nor-1 orphan steroid receptors in T-cell apoptosis. EMBO J. 1997 Apr 15;16(8):1865–75.
Cheng, L. E., et al. “Functional redundancy of the Nur77 and Nor-1 orphan steroid receptors in T-cell apoptosis.EMBO J, vol. 16, no. 8, Apr. 1997, pp. 1865–75. Pubmed, doi:10.1093/emboj/16.8.1865.
Cheng LE, Chan FK, Cado D, Winoto A. Functional redundancy of the Nur77 and Nor-1 orphan steroid receptors in T-cell apoptosis. EMBO J. 1997 Apr 15;16(8):1865–1875.

Published In

EMBO J

DOI

ISSN

0261-4189

Publication Date

April 15, 1997

Volume

16

Issue

8

Start / End Page

1865 / 1875

Location

England

Related Subject Headings

  • Transcriptional Activation
  • Transcription Factors
  • Thymus Gland
  • T-Lymphocytes
  • Spleen
  • Receptors, Thyroid Hormone
  • Receptors, Steroid
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Antigen, T-Cell
  • Protein Binding