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Nuclear factor of activated T cells (NFAT) is a family of transcription factors critical for gene expression in the immune system, especially for cytokine genes. The family consists of five members: NFATc1, NFATc2, NFATc3, NFATc4, and NFAT5. NFATc1–NFATc4 are regulated by calcium signaling via calcineurin, while NFAT5 responds to osmotic stress. Classical NFAT isoforms are activated by calcineurin-mediated dephosphorylation, leading to nuclear translocation and DNA binding. NFATs regulate cytokine production, T cell activation/differentiation, and play roles in development and disease. Immunosuppressive drugs like cyclosporin A and FK506 inhibit calcineurin, blocking NFAT activation and suppressing T-cell mediated immunity. Dysregulation is linked to autoimmune diseases, inflammatory disorders, cardiovascular diseases, neurodevelopmental disorders, and cancers.
Inhibition of calcineurin activity, blocking NFAT dephosphorylation and nuclear import
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