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Cell Death Dis. 2016 Apr 21;7:e2199. doi: 10.1038/cddis.2016.97.

Cell cycle and apoptosis regulation by NFAT transcription factors: new roles for an old player.

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Programa de Biologia Celular, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
Department of Signaling and Gene Expression, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
Laboratory for Proteomics and Protein Engineering, Carlos Chagas Institute, FIOCRUZ-Paraná, Brazil.
Department of Basic Sciences (FCB), Universidade Federal Fluminense, Nova Friburgo, Brazil.


The NFAT (nuclear factor of activated T cells) family of transcription factors consists of four Ca(2+)-regulated members (NFAT1-NFAT4), which were first described in T lymphocytes. In addition to their well-documented role in T lymphocytes, where they control gene expression during cell activation and differentiation, NFAT proteins are also expressed in a wide range of cells and tissue types and regulate genes involved in cell cycle, apoptosis, angiogenesis and metastasis. The NFAT proteins share a highly conserved DNA-binding domain (DBD), which allows all NFAT members to bind to the same DNA sequence in enhancers or promoter regions. The same DNA-binding specificity suggests redundant roles for the NFAT proteins, which is true during the regulation of some genes such as IL-2 and p21. However, it has become increasingly clear that different NFAT proteins and even isoforms can have unique functions. In this review, we address the possible reasons for these distinct roles, particularly regarding N- and C-terminal transactivation regions (TADs) and the partner proteins that interact with these TADs. We also discuss the genes regulated by NFAT during cell cycle regulation and apoptosis and the role of NFAT during tumorigenesis.

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