Retinoids enhance glucocorticoid-induced apoptosis of T cells by facilitating glucocorticoid receptor-mediated transcription

K. Tóth, Z. Sarang, B. Scholtz, P. Brázda, N. Ghyselinck, P. Chambon, L. Fésüs, Z. Szondy

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Glucocorticoid-induced apoptosis of thymocytes is one of the first recognized forms of programmed cell death. It was shown to require gene activation induced by the glucocorticoid receptor (GR) translocated into the nucleus following ligand binding. In addition, the necessity of the glucocorticoid-induced, but transcription-independent phosphorylation of phosphatidylinositol-specific phospholipase C (PI-PLC) has also been shown. Here we report that retinoic acids, physiological ligands for the nuclear retinoid receptors, enhance glucocorticoid-induced death of mouse thymocytes both in vitro and in vivo. The effect is mediated by retinoic acid receptor (RAR) alpha/retinoid X receptor (RXR) heterodimers, and occurs when both RARα and RXR are ligated by retinoic acids. We show that the ligated RARα/RXR interacts with the ligated GR, resulting in an enhanced transcriptional activity of the GR. The mechanism through which this interaction promotes GR-mediated transcription does not require DNA binding of the retinoid receptors and does not alter the phosphorylation status of Ser232, known to regulate the transcriptional activity of GR. Phosphorylation of PI-PLC was not affected. Besides thymocytes, retinoids also promoted glucocorticoid-induced apoptosis of various T-cell lines, suggesting that they could be used in the therapy of glucocorticoid-sensitive T-cell malignancies.

Original languageEnglish
Pages (from-to)783-792
Number of pages10
JournalCell Death and Differentiation
Volume18
Issue number5
DOIs
Publication statusPublished - May 2011

Fingerprint

Glucocorticoid Receptors
Retinoids
Glucocorticoids
Retinoid X Receptors
Apoptosis
T-Lymphocytes
Thymocytes
Phosphoinositide Phospholipase C
Retinoic Acid Receptors
Phosphorylation
Tretinoin
Ligands
Cytoplasmic and Nuclear Receptors
Transcriptional Activation
Cell Death
Cell Line
DNA
Neoplasms

Keywords

  • apoptosis
  • glucocorticoid
  • retinoid
  • T cells

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

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abstract = "Glucocorticoid-induced apoptosis of thymocytes is one of the first recognized forms of programmed cell death. It was shown to require gene activation induced by the glucocorticoid receptor (GR) translocated into the nucleus following ligand binding. In addition, the necessity of the glucocorticoid-induced, but transcription-independent phosphorylation of phosphatidylinositol-specific phospholipase C (PI-PLC) has also been shown. Here we report that retinoic acids, physiological ligands for the nuclear retinoid receptors, enhance glucocorticoid-induced death of mouse thymocytes both in vitro and in vivo. The effect is mediated by retinoic acid receptor (RAR) alpha/retinoid X receptor (RXR) heterodimers, and occurs when both RARα and RXR are ligated by retinoic acids. We show that the ligated RARα/RXR interacts with the ligated GR, resulting in an enhanced transcriptional activity of the GR. The mechanism through which this interaction promotes GR-mediated transcription does not require DNA binding of the retinoid receptors and does not alter the phosphorylation status of Ser232, known to regulate the transcriptional activity of GR. Phosphorylation of PI-PLC was not affected. Besides thymocytes, retinoids also promoted glucocorticoid-induced apoptosis of various T-cell lines, suggesting that they could be used in the therapy of glucocorticoid-sensitive T-cell malignancies.",
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AU - Tóth, K.

AU - Sarang, Z.

AU - Scholtz, B.

AU - Brázda, P.

AU - Ghyselinck, N.

AU - Chambon, P.

AU - Fésüs, L.

AU - Szondy, Z.

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