期刊
CELL COMMUNICATION AND SIGNALING
卷 10, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1478-811X-10-16
关键词
Activation induced cell death/AICD; Anergy; Apoptosis; Calcineurin; NFATc; NFATc1/alpha A; NF-kappa B; Proliferation
类别
资金
- German Research Foundation (DFG)
- University of Wuerzburg
- Deutsche Forschungsgemeinschaft [Transregio TR52]
- Wilhelm-Sander und Scheel foundations
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/alpha A, a short isoform of NFATc1, is strongly induced. Upon primary stimulation of lymphocytes the induction of NFATc1/alpha A takes place during the G1 phase of cell cycle. Due to an auto-regulatory feedback circuit high levels of NFATc1/alpha A 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/alpha A supports antigen-mediated proliferation and protects lymphocytes against rapid AICD. Whereas high concentrations of NFATc1/alpha A can also lead to apoptosis, in collaboration with NF-kappa B-inducing co-stimulatory signals they support the survival of mature lymphocytes in late phases after their activation. However, if dysregulated, NFATc1/alpha A appears to contribute to lymphoma genesis and - as we assume - to further disorders of the lymphoid system. While the molecular details of NFATc1/alpha A action and its contribution to lymphoid disorders have to be investigated, NFATc1/alpha A 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据