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 anal 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; anal 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 the NFAT: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.
Original language | English (US) |
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Pages (from-to) | 2476-2489 |
Number of pages | 14 |
Journal | Oncogene |
Volume | 20 |
Issue number | 19 REV. ISS. 2 |
DOIs | |
State | Published - Apr 30 2001 |
Externally published | Yes |
Keywords
- Fos
- Jun
- Nuclear factor of activated T cells
- Transcriptional regulation
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research