NFATc1/A: The other face of NFAT factors in lymphocytes

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Abstract

In effector T and B cells immune receptor signals induce within minutes a rise of intracellular Ca ++, the activation of the phosphatase calcineurin and the translocation of NFAT transcription factors from cytosol to nucleus. In addition to this first wave of NFAT activation, in a second step the occurrence of NFATc1/αA, a short isoform of NFATc1, is strongly induced. Upon primary stimulation of lymphocytes the induction of NFATc1/αA takes place during the G1 phase of cell cycle. Due to an auto-regulatory feedback circuit high levels of NFATc1/αA are kept constant during persistent immune receptor stimulation. Contrary to NFATc2 and further NFATc proteins which dampen lymphocyte proliferation, induce anergy and enhance activation induced cell death (AICD), NFATc1/αA supports antigenmediated proliferation and protects lymphocytes against rapid AICD. Whereas high concentrations of NFATc1/αA can also lead to apoptosis, in collaboration with NF-KB-inducing co-stimulatory signals they support the survival of mature lymphocytes in late phases after their activation. However, if dysregulated, NFATc1/αA appears to contribute to lymphoma genesis and as we assume to further disorders of the lymphoid system. While the molecular details of NFATc1/αA action and its contribution to lymphoid disorders have to be investigated, NFATc1/αA differs in its generation and function markedly from all the other NFAT proteins which are expressed in lymphoid cells. Therefore, it represents a prime target for causal therapies of immune disorders in future. © 2012 Serfling et al.; licensee BioMed Central Ltd.

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Serfling, E., Avots, A., Klein-Hessling, S., Rudolf, R., Vaeth, M., & Berberich-Siebelt, F. (2012). NFATc1/A: The other face of NFAT factors in lymphocytes. Cell Communication and Signaling, 10. https://doi.org/10.1186/1478-811X-10-16

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