title: NFATc1/αA: The other Face of NFAT Factors in Lymphocytes.
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 antigen-mediated proliferation and protects lymphocytes against rapid AICD. Whereas high concentrations of NFATc1/αA can also lead to apoptosis, in collaboration with NF-κB-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.
authors: Department of Molecular Pathology, Institute of Pathology, University of Würzburg, Josef-Schneider-Str 2, D-97080, Würzburg, Germany. serfling.e@mail.uni-wuerzburg.de.
authors: Edgar
authors: E
authors: Serfling
authors: Andris
authors: A
authors: Avots
authors: Stefan
authors: S
authors: Klein-Hessling
authors: Ronald
authors: R
authors: Rudolf
authors: Martin
authors: M
authors: Vaeth
authors: Friederike
authors: F
authors: Berberich-Siebelt