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Critical Reviews™ in Immunology
IF: 1.352 5-Year IF: 3.347 SJR: 1.022 SNIP: 0.55 CiteScore™: 2.19

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v17.i3-4.30
pages 301-323

Signals for Activation of the GM-CSF Promoter and Enhancer in T Cells

M. Frances Shannon
Gene Expression and Epigenomics Laboratory, Department of Genome Biology, The John Curtin School of Medical Research, Australian National University, Canberra, 2600 Australia; University of Canberra, Canberra, ACT 2601, Australia
L. S Coles
Division of Human Immunology, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Frome Rd, Adelaide, South Australia
M. A. Vadas
Division of Human Immunology, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Frome Rd, Adelaide, South Australia
P. N. Cockerill
Division of Human Immunology, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Frome Rd, Adelaide, South Australia

ABSTRACT

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-κB/rel and AP-1 families of transcription factors. In contrast to the promoter, the enhancer responds only to PMA and Ca2+ ionophore signals and binds NFAT/AP-I complexes that appear to mediate its function.


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