April 1, 1997Annual Review of Immunology
TRANSCRIPTION FACTORS OF THE NFAT FAMILY:Regulation and Function
Authors
Discussion
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Implication
Review demonstrates calcineurin-dependent regulation and cooperative DNA binding of NFAT proteins in immune cells, highlighting mechanisms targeted by immunosuppressive drugs.
Key Points
- To summarize the regulatory mechanisms, structural characteristics, and transcriptional cooperation of NFAT family proteins in controlling immune-response genes.
- Synthesized molecular and structural findings regarding NFAT family diversity and functional domains.
- Examined the calcium- and calcineurin-dependent signaling cascade controlling NFAT nuclear translocation and its disruption by immunosuppressive drugs.
- Analyzed cooperative DNA-binding mechanisms between NFAT and AP-1 transcription factor complexes at composite gene promoters.
- NFAT activation requires dephosphorylation by the phosphatase calcineurin, which binds a conserved N-terminal domain to drive nuclear translocation from the cytoplasm.
- Calcineurin inhibition by cyclosporin A and FK506 blocks NFAT nuclear entry, thereby halting inducible cytokine gene transcription.
- NFAT proteins share DNA-binding homology with Rel-family factors and cooperatively interact with AP-1 (Fos/Jun) complexes at composite promoter sites.
Cite This Study
Rao et al. (1997) studied this question.