雌激素受体对NFAT3转录活性的抑制作用。
Repression of NFAT3 transcriptional activity by estrogen receptors.
作者信息
Qin X, Wang X-H, Yang Z-H, Ding L-H, Xu X-J, Cheng L, Niu C, Sun H-W, Zhang H, Ye Q-N
机构信息
Department of Molecular Oncology, Beijing Institute of Biotechnology, 27 Tai-Ping Lu Rd, Beijing 100850, China.
出版信息
Cell Mol Life Sci. 2008 Sep;65(17):2752-62. doi: 10.1007/s00018-008-8273-1.
Nuclear factor of activated T cells 3 (NFAT3) activities have been implicated in many biological processes, such as breast cancer, cardiac hypertrophy, learning and memory, and adipocyte differentiation. However, how protein factors regulate NFAT3 transcriptional activity is poorly understood. Here, we report that regardless of estrogen, overexpression of estrogen receptor alpha and beta (ERalpha and ERbeta) suppresses NFAT3 transcriptional activity, whereas knockdown of endogenous ERalpha and ERbeta enhances the activity. Estrogen further enhances ER inhibition of NFAT3-dependent transcription. ERalpha and ERbeta interact with NFAT3 independently of the NFAT agonists phorbol myristate acetate (PMA) and ionomycin, and ERalpha is recruited to an NFAT3 target gene promoter. Phosphorylation of ERalpha at different sites differentially affects ERalpha modulation of NFAT3 transcriptional activity. These results suggest that ER may play a critical role in regulation of NFAT3 transcriptional activity.
活化T细胞核因子3（NFAT3）的活性与许多生物学过程有关，如乳腺癌、心肌肥大、学习与记忆以及脂肪细胞分化。然而，蛋白质因子如何调节NFAT3转录活性仍知之甚少。在此，我们报告，无论有无雌激素，雌激素受体α和β（ERα和ERβ）的过表达均会抑制NFAT3转录活性，而内源性ERα和ERβ的敲低则会增强该活性。雌激素进一步增强了ER对NFAT3依赖性转录的抑制作用。ERα和ERβ独立于NFAT激动剂佛波酯肉豆蔻酸酯乙酸酯（PMA）和离子霉素与NFAT3相互作用，并且ERα被招募至NFAT3靶基因启动子。ERα在不同位点的磷酸化对ERα对NFAT3转录活性的调节有不同影响。这些结果表明，ER可能在NFAT3转录活性的调节中起关键作用。
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