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 Lee, Mi Ock Lee

Research output: Contribution to journalArticle

41 Citations (Scopus)

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. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)545-554
Number of pages10
JournalExperimental Cell Research
Volume256
Issue number2
DOIs
StatePublished - May 1 2000
Externally publishedYes

Fingerprint

Retinoic Acid Receptors
Tretinoin
Transcriptional Activation
Apoptosis
Transcription Factor AP-1
Serum Response Factor
Retinoids
T-Lymphocytes
Nuclear Receptor Subfamily 4, Group A, Member 1
T-Cell Leukemia
Trans-Activators
DNA
Hybridomas
Thymocytes
Reporter Genes
Blood Cells
Proteins
Yeasts
Genes

Keywords

  • Apoptosis
  • Nur77
  • RAR
  • Retinoic acid
  • RXR
  • T-lymphocytes

ASJC Scopus subject areas

  • Cell Biology

Cite this

Retinoic acid and its receptors repress the expression and transactivation functions of Nur77 : A possible mechanism for the inhibition of apoptosis by retinoic acid. / Kang, Hyo Jin; Song, Mi Ryoung; Lee, Soo-Kyung; Shin, Eui Chul; Choi, Youn Hee; Kim, Se Jong; Lee, Jae; Lee, Mi Ock.

In: Experimental Cell Research, Vol. 256, No. 2, 01.05.2000, p. 545-554.

Research output: Contribution to journalArticle

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