Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

The mechanism by which the human T-cell leukemia viruses type I and II (HTLV-I and -II) transform T cells is unknown, but the nonstructural Tax protein that these viruses produce is known to be essential for viral replication and to have the capacity to trans-activate cellular gene expression. The HTLV-I and -II Tax proteins have been shown to activate the promoter of both the human and mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) genes in mature T-cell lines. T-cell-specific Tax-responsive sequences were previously localized to the 90-bp region extending from base pairs -53 to +37 in the human GM-CSF promoter. In this study, a series of site-directed and deletion mutations were created in the human GM-CSF promoter, which was linked to the chloramphenicol acetyltransferase (CAT) gene, and the constructs were assayed for their response to Tax by using a Tax-expressing plasmid in transient cotransfection assays. The results demonstrated that both copies of the repeated sequence CATTA (A/T), located between base pairs -48 and -36, are required for Tax responsiveness in T cells and that these sequences bind nuclear factors present in T cells. The Tax-responsiveness of other sequences located 5' of base pair -53 was also examined, including an NF-kappa B consensus sequence and the CK1, CK2, and GC-rich regions identified in both the mouse and human GM-CSF promoters. These sequences did not have Tax-responsive regulatory activity when they were examined in the context of the intact human GM-CSF promoter in T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tax responsiveness of the GM-CSF promoter is mediated by mitogen-inducible sequences other than kappa B. 176 53

Transfected Jurkat cells overexpressing extracellular signal-regulated kinase (ERK1), also referred to as mitogen-activated protein (MAP) kinase, were selected by Western blotting assay using anti-ERK1 and antiphosphotyrosine antibodies in combination with a functional MAP kinase assay. We then asked whether enhanced ERK1 expression had any effect on induction of T-cell cytokine genes. The results show that overexpression of ERK1 enhances expression of T-cell interleukin-2 (IL-2), IL-3, and granulocyte-macrophage colony-stimulating factor mRNA; no change was seen in expression of the alpha-actin gene. DNA-binding activities of the transcription factors AP1, NF-AT, and NF-kB were specifically increased twofold to fourfold in ERK1-overexpressing clones relative to nontransformed or vector-transformed cells, whereas no enhancement of CK1-CK2 protein DNA binding activity was detected after ERK1 overexpression. Additionally, increased NF-AT DNA binding activity was associated with functional enhancement of NF-AT transactivating activity in ERK1-overexpressing cells. These results provide direct evidence for the role of MAP kinase in the regulation of cytokine gene expression and indicate that such regulation is likely mediated through the enhanced DNA binding activity of specific nuclear transcription factors.
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PMID:Overexpression of mitogen-activated protein kinase (ERK1) enhances T-cell cytokine gene expression: role of AP1, NF-AT, and NF-KB. 840 Feb 95