Publication: Regulation of NFAT by poly(ADP-ribose) polymerase activity in T cells
Authors
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
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Publisher
Elsevier
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DOI
https://doi.org/10.1016/j.molimm.2007.10.044
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info:eu-repo/semantics/article
Description
©2007. This document is the published, version of a Published Work that appeared in final form in Molecular Immunology. To access the final edited and published work see https://doi.org/10.1016/j.molimm.2007.10.044
Abstract
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.
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Citation
Molecular Immunology 45 (2008) 1863–1871
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