NFATC2 transcription factor regulates cell cycle progression during lymphocyte activation: evidence of its involvement in the control of cyclin gene expression
NFATC2 transcription factor regulates cell cycle progression during lymphocyte activation: evidence of its involvement in the control of cyclin gene expression
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DOI：
10.1096/fj.02-0282fje
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发表时间：
2002-10-01
期刊：
影响因子：
4.8
通讯作者：
Viola, JPB
中科院分区：
文献类型：
--
作者：
Caetano, MS;Vieira-De-Abreu, A;Viola, JPB
在抗原刺激下，淋巴细胞进入细胞周期并增殖，并且大多数活化的T细胞通过凋亡而死亡。许多调节淋巴细胞活化的蛋白质受属于NEAT家族的转录因子的控制。如前所述，NFATC 2-/-小鼠始终显示淋巴细胞增殖显著增加。在这里，我们评估NFATC 2在调节淋巴细胞增殖和参与控制淋巴细胞活化过程中的细胞周期进程中的作用。与NFATC 2 +/+细胞相比，NFATC 2/-淋巴细胞，包括CD 4（+）T细胞和B细胞，在刺激后过度增殖。细胞死亡的分析表明，NFATC 2-/-淋巴细胞在抗原刺激后除了过度增殖外，还显示出凋亡率增加。抗原刺激后的细胞周期分析显示，与NFATC 2 +/+培养物相比，NFATC 2-/-培养物含有更多的循环细胞，这与活化后细胞分裂时间的缩短有关。此外，NFATC 2-/-淋巴细胞的过度增殖与细胞周期蛋白A2、B1、E和F的过表达相关。两者合计，我们的研究结果表明，NFATC 2转录因子在控制淋巴细胞活化过程中的细胞周期中起着重要的作用，并可能作为正常细胞中的细胞增殖抑制剂。
Upon antigen stimulation, lymphocytes enter in cell cycle and proliferate, and most of the activated T cells die by apoptosis. Many of the proteins that regulate lymphocyte activation are under the control of transcription factors belonging to the NEAT family. As previously demonstrated, NFATC2-/- mice consistently showed a marked increase in lymphocyte proliferation. Here, we evaluate the role of NFATC2 in regulating lymphocyte proliferation and its involvement in the control of cell cycle progression during lymphocyte activation. NFATC2/- lymphocytes, including CD4(+) T cells and B cells, hyperproliferated upon stimulation when compared with NFATC2+/+ cells. Analysis of cell death demonstrated that NFATC2-/- lymphocytes displayed an increased rate of apoptosis after antigen stimulation in addition to the hyperproliferation. Cell cycle analysis after antigen stimulation showed that NFATC2-/- cultures contained more cycling cells when compared with NFATC2+/+ cultures, which is related to a shortening in time of cell division upon activation. Furthermore, hyperproliferation of NFATC2-/- lymphocytes is correlated to an overexpression of cyclins A2, B1, E, and F. Taken together, our results suggest that the NFATC2 transcription factor plays an important role in the control of cell cycle during lymphocyte activation and may act as an inhibitor of cell proliferation in normal cells.