Partners in transcription: NFAT and AP-1
- PMID: 11402342
- DOI: 10.1038/sj.onc.1204386
Partners in transcription: NFAT and AP-1
Abstract
Combinatorial regulation is a powerful mechanism that enables tight control of gene expression, via integration of multiple signaling pathways that induce different transcription factors required for enhanceosome assembly. The four calcium-regulated transcription factors of the NFAT family act synergistically with AP-1 (Fos/Jun) proteins on composite DNA elements which contain adjacent NFAT and AP-1 binding sites, where they form highly stable ternary complexes to regulate the expression of diverse inducible genes. Concomitant induction of NFAT and AP-1 requires concerted activation of two different signaling pathways: calcium/calcineurin, which promotes NFAT dephosphorylation, nuclear translocation and activation; and protein kinase C (PKC)/Ras, which promotes the synthesis, phosphorylation and activation of members of the Fos and Jun families of transcription factors. A fifth member of the NFAT family, NFAT5, controls the cellular response to osmotic stress, by a mechanism that requires dimer formation and is independent of calcineurin or of interaction with AP-1. Pharmacological interference with theNFAT:AP-1 interaction may be useful in selective manipulation of the immune response. Balanced activation of NFAT and AP-1 is known to be required for productive immune responses, but the role of NFAT:AP-1 interactions in other cell types and biological processes remains to be understood.
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