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)

Human T-cell lymphotropic virus type I (HTLV-I), the cause of adult T-cell leukemia, is also associated with the neurological disease, TSP/HAM (tropical spastic paraparesis/HTLV-I associated myelopathy). The HTLV-I genome encodes a protein, Tax, that trans activates viral and cellular gene transcription. To understand the mechanisms for the production of cytokines by HTLV-I in nervous tissue, we examined their expression in glial cells which carried the Tax-expressing vector. We demonstrated that Tax expression enhanced the production by glial cells of interleukin (IL)-1, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor (TGF) beta. We suggest that the excessive production of cytokines in nervous tissue may play a role in pathogenesis of TSP/HAM. Glial cells that carry the tax gene may provide a model useful for in vitro study of the mechanism of production of cytokines in the nervous system.
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PMID:Induction of cytokines in glial cells by trans activator of human T-cell lymphotropic virus type I. 142 68

Human T-cell leukemia virus type 1 (HTLV-1) induces adult T-cell leukemia and also a neurological disease, tropical spastic paraparesis. Tax protein (p40tax) of HTLV-1 activates in trans its own transcriptional enhancer in the long terminal repeat and also those in some cellular genes such as interleukin 2 receptor alpha, granulocyte-macrophage colony-stimulating factor, Fos, Jun and MHC class I. Thus, Tax has been proposed to play a critical role in the pathogenesis induced by HTLV-1 infection. Here, we report formation of a complex of Tax protein with the precursor protein p105 of the NF-kappa B p50 subunit. p105 was co-immunoprecipitated with Tax protein from cells infected with HTLV-1 from cells transfected with the Tax expression plasmid, but not from cells transfected with inactive mutants of Tax. Furthermore, a GST-p105 fusion protein produced in Escherichia coli bound to Tax protein. These results strongly suggest that the trans-activator Tax protein forms a complex with precursor NF-kappa B p105 and plays a role in trans-activation of transcriptional initiation.
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PMID:Transcriptional activator Tax of HTLV-1 binds to the NF-kappa B precursor p105. 150 85

Many cell signals such as CD28 and CD4 binding can costimulate cytokine gene expression in activated T cells. We have found that the human T leukemia/lymphotropic virus type 1 viral protein Tax can also strongly costimulate expression of interleukin-2 (IL-2), IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA in T cells activated with the phorbol ester phorbol myristate acetate (PMA) and calcium ionophore, which can mimic activation through the antigen specific T-cell receptor. Reporter constructs also showed strong synergy between both stimuli and showed that Tax and the PMA-Ca2+ ionophore act through different regions of the IL-2 and GM-CSF genes. Furthermore, the Tax-responsive regions (TxRR) from both GM-CSF and IL-2 respond to costimulation through the CD28 surface receptor. The GM-CSF and IL-2 TxRRs showed significantly higher levels of NF-kappaB/rel binding, following induction by Tax, compared with that of the PMA-Ca2+ ionophore with only Tax capable of inducing c-Rel binding to a Consensus kappaB element within the GM-CSF TxRR. Tax protein mutants, however, showed that a pathway(s) other than NF-kappaB/rel induction could also cooperate with the PMA-Ca2+ ionophore to activate the GM-CSF and IL-2 genes. This high-level costimulation by Tax, through multiple pathways, may be important in the early stages of leukemia and in the nervous system disorder tropical spastic paraparesis.
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PMID:Costimulation of cytokine gene expression in T cells by the human T leukemia/lymphotropic virus type 1 trans activator Tax. 864 37