期刊
EMBO JOURNAL
卷 19, 期 17, 页码 4783-4795出版社
WILEY
DOI: 10.1093/emboj/19.17.4783
关键词
activation-induced cell death; AP-1; cytokine expression; nuclear factor of activated T cells; transcriptional regulation
资金
- NATIONAL CANCER INSTITUTE [R37CA042471, R01CA042471] Funding Source: NIH RePORTER
- NCI NIH HHS [R01 CA042471, R37 CA042471, CA42471] Funding Source: Medline
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. sere 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, MIP1 alpha and Fas ligand mRNAs is absolutely dependent on cooperation between NFAT and Fos-Jun; in contrast, NFAT induces tumor necrosis factor alpha (TNF alpha) 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.
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