NFATc2-mediated repression of cyclin-dependent kinase 4 expression
NFATc2-mediated repression of cyclin-dependent kinase 4 expression
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DOI：
10.1016/s1097-2765(02)00701-3
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发表时间：
2002-11-01
期刊：
影响因子：
16
通讯作者：
Burakoff, SJ
中科院分区：
文献类型：
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作者：
Baksh, S;Widlund, HR;Burakoff, SJ
钙调神经磷酸酶调节的转录因子，活化T细胞的核因子（NFAT），控制T细胞功能的许多方面。在这里，我们证明了钙调神经磷酸酶/NFAT途径负调控细胞周期蛋白依赖性激酶4（CDK 4）的表达。一个典型的NFAT结合位点被确定，并发现是敏感的钙信号，FK 506/CsA，和组蛋白脱乙酰酶活性，并不需要AP-1。NFATc 2的异位表达抑制人CDK 4启动子的基础活性。此外，钙调磷酸酶A α（-/-）和NFATc 2（-/-）小鼠的CDK 4蛋白水平均升高，证实了钙调磷酸酶/NFAT途径的负调节作用。因此，该途径可以在转录水平上调节CDK 4的表达，并控制细胞如何重新进入静息、非增殖状态。
The calcineurin-regulated transcription factor, nuclear factor of activated T cells (NFAT), controls many aspects of T cell function. Here, we demonstrate that the calcineurin/NFAT pathway negatively regulates the expression of cyclin-dependent kinase 4 (CDK4). A canonical NFAT binding site was identified and found to be sensitive to calcium signals, FK506/CsA, and histone deacetylase activity and to not require AP-1. Ectopic expression of NFATc2 inhibited the basal activity of the human CDK4 promoter. Additionally, both calcineurin Aalpha(-/-) and NFATc2(-/-) mice had elevated protein levels of CDK4, confirming a negative regulatory role for the calcineurin/NFAT pathway. This pathway may thus regulate the expression of CDK4 at the transcriptional level and control how cells re-enter a resting, nonproliferative state.