Repression of NFAT3 transcriptional activity by estrogen receptors

Abstract.

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