NFAT proteins

Originally described in the immune system, NFAT proteins comprise a family of transcriptional factors that play key roles in many cellular processes that control not only immune responses but also the development, regulation, and differentiation of many other tissues. Activation of NFAT proteins results in the expression of specific sets of genes that regulate multiple cell functions [1,2]. 

The activation of NFAT is regulated by calcium. In resting cells, NFAT proteins localize in the cytoplasm... 

The role of NFAT in the immune system is not restricted to T cells. NFAT proteins are also expressed in other cells of the immune system, such as B cells, NK cells, and mast cells, where they have been shown to regulate the expression of cytokines, cell surface receptors, and immunoglobulins [4, 5]. 

NFAT proteins are expressed in skeletal, cardiac, and smooth muscle and play important roles in the regulation of the development and differentiation of these tissues. In skeletal muscle, NFAT isoforms are expressed at different stages of development and regulate progression from early muscle cell precursors to mature myocytes. NFAT proteins have also been shown to control the expression of the myosin heavy chain and positively regulate muscle growth [1, 2]. 

NFAT2 plays a key role in the development of the embryo s heart. In the precursor cells, there is a temporal and spatial specific expression of NFAT2, which directs the formation of the valves and the septum in the heart. In the adult heart, NFAT proteins also cooperate with transcription factors of the GATA and MEF2 families to regulate cardiac muscle hypertrophic responses. 

The development of drugs that block Calcineuiin phosphatase activity has allowed successful prevention of graft rejection. Due to the key role that NFAT has in T-cell activation, these inhibitors behave as potent immunosuppressors. Nevertheless, the important roles that NFAT proteins have in other tissues suggest that exploring the use of similar drugs in other pathological contexts may be clinically and therapeutically relevant. 

Macian F (2005) NFAT proteins key regulators of T-cell development and function. Nat Rev Immunol 5 472-484... 

The expression of genes involved in cell proliferation and cell death is regulated by nuclear transcriptional factors. NFAT (Nuclear Factor of Activated T cells) proteins are a family of Ca2+-dependent transcription factors (Crabtree, 2001), whose nuclear translocation and transcriptional activity is regulated by Ca2+/calmodulin-dependent protein phosphatase, calcineurin (Crabtree, 2001). Thus, NFAT proteins can potentially be activated by diverse stimuli that lead to increased intracellular calcium levels. The NF-kB (nuclear factor kappa B) family... 

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