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Partners in transcription: NFAT and AP-1 Macian F; Lopez-Rodriguez C; Rao AOncogene 2001[Apr]; 20 (19): 2476-89Combinatorial 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.|*Nuclear Proteins[MESH]|Animals[MESH]|Cytokines/biosynthesis/genetics[MESH]|DNA-Binding Proteins/chemistry/*physiology[MESH]|DNA/metabolism[MESH]|Macromolecular Substances[MESH]|Models, Molecular[MESH]|NFATC Transcription Factors[MESH]|Response Elements[MESH]|Signal Transduction[MESH]|T-Lymphocytes/immunology[MESH]|Transcription Factor AP-1/chemistry/*physiology[MESH]|Transcription Factors/chemistry/*physiology[MESH]|Transcriptional Activation[MESH] |
