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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

 Hyo-Jin Kang  ;  Mi-Ryoung Song  ;  Soo-Kyung Lee  ;  Eui-Chul Shin  ;  Youn-Hee Choi  ;  Se Jong Kim  ;  Jae Woon Lee  ;  Mi-Ock Lee 
 Experimental Cell Research, Vol.256(2) : 545-554, 2000 
Journal Title
 Experimental Cell Research 
Issue Date
Amino Acid Motifs ; Apoptosis/physiology* ; DNA/metabolism ; DNA-Binding Proteins/metabolism* ; Humans ; Jurkat Cells ; Nuclear Receptor Subfamily 4, Group A, Member 1 ; Protein Binding ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Receptors, Retinoic Acid/metabolism ; Receptors, Retinoic Acid/physiology* ; Receptors, Steroid ; T-Lymphocytes/cytology* ; Transcription Factors/metabolism* ; Transfection ; Tretinoin/metabolism ; Tretinoin/pharmacology ; Tretinoin/physiology* ; Two-Hybrid System Techniques
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 RARalpha or RXRalpha. Nur77 bound RARalpha or RXRalpha 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.
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1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Se Jong(김세종)
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