Repression of NFAT3 transcriptional activity by estrogen receptors

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 (ER alpha and ER beta) suppresses NFAT3 transcriptional activity, whereas knockdown of endogenous ER alpha and ER beta enhances the activity. Estrogen further enhances ER inhibition of NFAT3-dependent transcription. ER alpha and ER beta interact with NFAT3 independently of the NFAT agonists phorbol myristate acetate (PMA) and ionomycin, and ER alpha is recruited to an NFAT3 target gene promoter. Phosphorylation of ER alpha at different sites differentially affects ER alpha modulation of NFAT3 transcriptional activity. These results suggest that ER may play a critical role in regulation of NFAT3 transcriptional activity.