Regulation of NFAT by poly (ADP-ribose) polymerase activity in T cells
Fiche publication
Date publication
avril 2008
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SCHREIBER Valérie
Tous les auteurs :
Valdor R, Schreiber V, Saenz L, Martinez T, Munoz-Suano A, Dominguez-Villar M, Ramirez P, Parrilla P, Aguado E, Garcia-Czar F, Yelamos J
Lien Pubmed
Résumé
The nuclear factor of activated T cells (NFAT) family of transcription factors is pivotal for T lymphocyte functionality. All relevant NFAT activation events upon T cells stimulation such as nuclear translocation, DNA binding, and transcriptional activity have been shown to be dictated by its phosphorylation state. Here, we provide evidence for a novel post-translational modification that regulates NFAT. Indeed, NFATc1 and NFATc2 are poly(ADP-ribosyl)ated by poly-ADP-ribose polymerase-1 (PARP-1). Moreover, we have also found a physical interaction between PARP-1 and both NFATc1 and NFATc2. Interestingly, PARP is activated during T cell stimulation in the absence of DNA damage, leading to ADP-ribose polymers formation and transfer to nuclear acceptor proteins. Our data suggest that poly(ADP-ribosyl)ation modulates the activation of NFAT in T cells, as PARP inhibition causes an increase in NFAT-dependent transactivation and a delay in NFAT nuclear export. Poly(ADP-ribosyl)ation will expedited NFAT export from the nucleus directly or by priming/facilitating NFAT phosphorylation. Altogether, these data point to PARP-1 and poly(ADP-ribosyl)ation as a novel regulatory mechanism of NFAT at nuclear level, suggesting a potential use of PARP as a new therapeutic target in the modulation of NFAT.
Référence
Mol Immunol. 2008 Apr;45(7):1863-71.