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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of T helper cells results in coordinate expression of a number of cytokines involved in differentiation, proliferation and activation of the haematopoietic system. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is one such cytokine whose increased expression results partly from increases in transcription. Cis-acting elements with NF kappa B, AP-1 and ETS-like motifs have been identified in the promoter region of the GM-CSF gene, which are important for transcriptional activity following PMA and ionomycin stimulation. A number of the ETS family of transcription factors are expressed in T cells, including ETS1 and ELF1. Here we describe the ability of these factors to interact with a site (GM5), located within the CLE0 element, -47 to -40 upstream of the GM-CSF transcription initiation site. Exogenous ETS1, but not ELF1, can transactivate GM-CSF, through the GM5 site, in a PMA/ionomycin dependent manner. Other unidentified ETS-like factors present in Jurkat cells are also capable of binding GM5. Mutation of the core ETS binding site from -GGAA- to -GGAT- prevents the binding of ETS-like factors with the exception of ETS1. The GM-CSF promoter, modified in this way to be ETS1 specific, is fully responsive to PMA/ionomycin induction, in addition to ETS1 transactivation in the presence of PMA and ionomycin. Together these data suggest that ETS1 may be involved in mediating the increased GM-CSF production associated with T cell activation.
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PMID:ETS1 transactivates the human GM-CSF promoter in Jurkat T cells stimulated with PMA and ionomycin. 747 34

The tumor necrosis factor-alpha-responsive region of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) promoter (-114 to -31) encompasses binding sites for NF-kappaB, CBF, AP-1, ETS, and NFAT families of transcription factors. We show both here and previously that mutation of any one of these binding sites greatly reduces tumor necrosis factor-alpha induction of the GM-CSF promoter. Interspersed between these elements are sequences that when mutated lead to an increase in GM-CSF promoter activity. We have previously shown that two of these repressor elements bind proteins known as cold shock domain (CSD) factors and that overexpression of CSD proteins leads to repression of GM-CSF promoter activity in fibroblasts. CSD proteins are single strand DNA- and RNA-binding proteins that contact 5'-CCTG-3' sequences in the GM-CSF repressor elements. We show here that two newly identified repressor sequences in the proximal promoter can also bind CSD proteins. We have characterized the CSD-containing protein complexes that bind to the GM-CSF promoter and identified a novel protein related to mitochondrial single strand binding protein that forms part of one of these complexes. The four CSD-binding sites on the promoter occur in pairs on opposite strands of the DNA and appear to form an ordered array of binding elements. A similar ordered array of CSD sites are present in the promoters of the granulocyte colony-stimulating factor and interleukin-3 genes, implying a common mechanism for negative regulation of these myeloid growth factors.
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PMID:An ordered array of cold shock domain repressor elements across tumor necrosis factor-responsive elements of the granulocyte-macrophage colony-stimulating factor promoter. 1079 31

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine expressed in the non-small lung carcinoma cells (NSCLC). However, transcriptional regulation of GM-CSF is not well characterized in NSCLC. In this study we found that two cis-acting ETS family consensus sites are important for transcriptional regulation of GM-CSF in A549 human lung carcinoma cells. These two sites are located separately at around -40 and -100 bp from the transcription start site. Results of transient transfection assays with A549 cells indicated that ETS2 had a strong positive effect on GM-CSF promoter activity. Furthermore, this activity was enhanced by protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), in an ETS consensus-dependent manner, while PMA could also enhance the expression level of ETS2. The protein kinase C inhibitors decreased GM-CSF promoter activity induced by the protein kinase C activator PMA. We also found that antisense ETS2 mRNA decreased PMA-induced GM-CSF promoter activity, supporting the possibility that ETS2 is involved in protein kinase C-induced GM-CSF transcriptional function. Endogenous expression of GM-CSF mRNA was increased by ETS2 transfection and the increased expression was further enhanced by PMA. These data indicate that GM-CSF is up-regulated by ETS2, a target of protein kinase C.
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PMID:ETS2 is involved in protein kinase C-activated expression of granulocyte-macrophage colony-stimulating factor in human non-small lung carcinoma cell line, A549. 1264 85