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Retinoic acid and its receptors repress the expression and transactivation functions of Nur77: a possible mechanism for the inhibition of apoptosis by retinoic acid
- Source :
- Experimental cell research. 256(2)
- Publication Year :
- 2000
-
Abstract
- Nur77 (NGFI-B) is an orphan nuclear receptor that has been implicated in activation-induced T-cell apoptosis. Retinoids, potent immune modulators, were shown to inhibit the activation-induced apoptosis of immature thymocytes and T-cell hybridomas. To illustrate the mechanism of the inhibition, we examined the effects of retinoic acid (RA) on the expression and transactivation functions of Nur77 in the human peripheral blood mononuclear cells and the human T-cell leukemia, Jurkat. All- trans -RA remarkably repressed the DNA binding and transcriptional induction of Nur77. Among the two potential trans -acting factors that activate Nur77 gene promoter, i.e., AP-1 and related serum response factor (RSRF), all- trans -RA repressed DNA binding and reporter gene activity of AP-1 but not that of RSRF, suggesting that the inhibition may be mediated through AP-1. We also demonstrated a posttranscriptional regulation of Nur77 function by retinoid receptors by showing that transactivation activity of Nur77 was significantly inhibited by cotransfection of RARα or RXRα. Nur77 bound RARα or RXRα in both yeast and mammalian two-hybrid tests, suggesting that direct protein–protein interaction between these receptors may mediate the inhibition. Taken all together, we demonstrated that RA repressed Nur77 function through multiple mechanisms that may provide the basis for RA inhibition on the apoptosis of activated T-lymphocytes.
- Subjects :
- Receptors, Steroid
Nerve growth factor IB
Receptors, Retinoic Acid
T-Lymphocytes
Amino Acid Motifs
Retinoic acid
Receptors, Cytoplasmic and Nuclear
Apoptosis
Tretinoin
Biology
Retinoid X receptor
Transfection
Jurkat cells
chemistry.chemical_compound
Transactivation
Jurkat Cells
Two-Hybrid System Techniques
Serum response factor
Nuclear Receptor Subfamily 4, Group A, Member 1
Humans
Receptor
Cell Biology
DNA
Molecular biology
DNA-Binding Proteins
Nuclear receptor
chemistry
Protein Binding
Transcription Factors
Subjects
Details
- ISSN :
- 00144827
- Volume :
- 256
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Experimental cell research
- Accession number :
- edsair.doi.dedup.....aac0e11877759b35d202a943edd8a0e3