Gene expression elicited by NFAT in the presence or absence of cooperative recruitment of Fos and Jun

Fernando Macián, Carmen García-Rodríguez, Anjana Rao

Research output: Contribution to journalArticle

243 Scopus citations

Abstract

Cooperation between nuclear factor of activated T cells (NFAT) and AP-1 (Fos-Jun) proteins on composite NFAT-AP-1 DNA elements constitutes a powerful mechanism for signal integration of the calcium and protein kinase C/Ras pathways in the regulation of gene expression. Here we report that NFAT can induce expression of certain genes in T cells without the need for cooperative recruitment of Fos and Jun. Using NFAT1 mutant proteins that are unable to interact with Fos-Jun dimers but are unaffected in DNA binding or transcriptional activity, we show that expression of interleukin (IL)-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, IL-4, MIP1α and Fas ligand mRNAs is absolutely dependent on cooperation Between NFAT and Fos-Jun; in contrast, NFAT induces tumor necrosis factor α (TNFα) mRNA and IL-13 promoter activity without any necessity to recruit Fos and Jun. Furthermore, we show that NFAT-Fos-Jun cooperation is also essential to elicit the NFAT-dependent program of activation-induced cell death. Our results support the hypothesis that even in a single cell type, NFAT activation can evoke two distinct biological programs of gene expression, dependent or independent of NFAT-AP-1 cooperation.

Original languageEnglish (US)
Pages (from-to)4783-4795
Number of pages13
JournalEMBO Journal
Volume19
Issue number17
DOIs
StatePublished - Sep 1 2000
Externally publishedYes

Keywords

  • AP-1
  • Activation-induced cell death
  • Cytokine expression
  • Nuclear factor of activated T cells
  • Transcriptional regulation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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