Browsing by Subject "Poly-ADP ribose polymerases"

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    Regulation of NFAT by poly(ADP-ribose) polymerase activity in T cells
    (Elsevier, 2007-10-31) Schreiber, Valerie; Saenz, Luis; Martínez, Teresa; Munoz Suano, Alba; Dominguez Villar, Margarita; Ramírez, Pablo; Parrilla, Pascual; Aguado, Enrique; García Cózar, Francisco; Yélamos, José; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
    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(ADPribosyl)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.