Signals for activation of the GM-CSF promoter and enhancer in T cells.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is one of the many cytokines produced following T-cell activation. It is also produced in a variety of other cell types, in particular following activation by inflammatory mediators. Changes in the rate of transcription are important in the control of GM-CSF expression in T cells and in fibroblasts and endothelial cells. The GM-CSF gene contains two distinct transcriptional control regions. These are the proximal promoter consisting of the first 120 bp from the transcription start site and an enhancer located approximately 3 kb upstream from the proximal promoter. Distinct regions of the proximal promoter respond to a wide array of signals such as phorbol myristate acetate (PMA) and Ca2+ ionophore or phytohemaglutinin (PHA), CD28 activation, human T leukemia virus (HTLV)-1 tax, TNF, and interleukin 1 (IL-1). The transcription factors that mediate these responses have mainly been defined, with the major inducible proteins being the NF-kappa B/rel and AP-I families of transcription factors. In contrast to the promoter, the enhancer responds only to PMA and Ca2+ ionophore signals and binds NFAT/AP-1 complexes that appear to mediate its function.
Shannon
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MF
Division of Human Immunology, Hanson Centre for Cancer Research, Adelaide, South Australia.
Coles
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LS
Vadas
M A
MA
Cockerill
P N
PN
D000818:Animals; D004742:Enhancer Elements, Genetic / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics* / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D016178:Granulocyte-Macrophage Colony-Stimulating Factor