- search hit 1 of 1
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.…
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): | CC BY: Creative-Commons-Lizenz: Namensnennung |