Partners in transcription: NFAT and AP-1

F. Macián, C. López-Rodríguez, A. Rao

Research output: Contribution to journalReview article

542 Scopus citations

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 languageEnglish (US)
Pages (from-to)2476-2489
Number of pages14
JournalOncogene
Volume20
Issue number19 REV. ISS. 2
DOIs
StatePublished - Apr 30 2001
Externally publishedYes

Keywords

  • Fos
  • Jun
  • Nuclear factor of activated T cells
  • Transcriptional regulation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Macián, F., López-Rodríguez, C., & Rao, A. (2001). Partners in transcription: NFAT and AP-1. Oncogene, 20(19 REV. ISS. 2), 2476-2489. https://doi.org/10.1038/sj.onc.1204386