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NFATc1/alphaA: The other Face of NFAT Factors in Lymphocytes

Please always quote using this URN: urn:nbn:de:bvb:20-opus-75748
  • 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 ofIn 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-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.show moreshow less

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Metadaten
Author: Edgar Serfling, Andris Avots, Stefan Klein-Hessling, Ronald Rudolf, Martin Vaeth, Friederike Berberich-Siebelt
URN:urn:nbn:de:bvb:20-opus-75748
Document Type:Review
Faculties:Medizinische Fakultät / Pathologisches Institut
Language:English
Year of Completion:2012
Source:In: Cell Communication and Signaling (2012) 10: 16, doi:10.1186/1478-811X-10-16
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
GND Keyword:Medizin
Tag:Activation induced cell death/AICD; Anergy; Apoptosis; Calcineurin; NF-κB; NFATc; NFATc1/αA; Proliferation
Release Date:2013/04/11
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2012
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung