FasL expression in activated T lymphocytes involves HuR-mediated stabilization

Gillian L. Drury, Sergio Di Marco, Virginie Dormoy-Raclet, Julie Desbarats, Imed Gallouzi

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

A prolonged activation of the immune system is one of the main causes of hyperproliferation of lymphocytes leading to defects in immune tolerance and autoimmune diseases. Fas ligand (FasL), a member of the TNF superfamily, plays a crucial role in controlling this excessive lymphoproliferation by inducing apoptosis in T cells leading to their rapid elimination. Here, we establish that posttranscriptional regulation is part of the molecular mechanisms that modulate FasL expression, and we show that in activated T cells FasL mRNA is stable. Our sequence analysis indicates that the FasL 3′-untranslated region (UTR) contains two AU-rich elements (AREs) that are similar in sequence and structure to those present in the 3′-UTR of TNFα mRNA. Through these AREs, the FasL mRNA forms a complex with the RNA-binding protein HuR both in vitro and ex vivo. Knocking down HuR in HEK 293 cells prevented the phorbol 12-myristate 13-acetate-induced expression of a GFP reporter construct fused to the FasL 3′-UTR. Collectively, our data demonstrate that the posttranscriptional regulation of FasL mRNA by HuR represents a novel mechanism that could play a key role in the maintenance and proper functioning of the immune system.

Original languageEnglish
Pages (from-to)31130-31138
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number41
DOIs
Publication statusPublished - 8 Oct 2010
Externally publishedYes

Fingerprint

Fas Ligand Protein
T-cells
Stabilization
T-Lymphocytes
3' Untranslated Regions
AU Rich Elements
Messenger RNA
Immune system
Immune System
Immune Tolerance
RNA-Binding Proteins
Lymphocytes
HEK293 Cells
Immune System Diseases
Autoimmune Diseases
Sequence Analysis
Acetates
Chemical activation
Maintenance
Apoptosis

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

FasL expression in activated T lymphocytes involves HuR-mediated stabilization. / Drury, Gillian L.; Di Marco, Sergio; Dormoy-Raclet, Virginie; Desbarats, Julie; Gallouzi, Imed.

In: Journal of Biological Chemistry, Vol. 285, No. 41, 08.10.2010, p. 31130-31138.

Research output: Contribution to journalArticle

Drury, Gillian L. ; Di Marco, Sergio ; Dormoy-Raclet, Virginie ; Desbarats, Julie ; Gallouzi, Imed. / FasL expression in activated T lymphocytes involves HuR-mediated stabilization. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 41. pp. 31130-31138.
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