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The granulocyte-macrophage colony-stimulating factor promoter cis-acting element CLE0 mediates induction signals in T cells and is recognized by factors related to AP-1 (1993)

by E S Masuda, H Tokumitsu, A Tsuboi, J Shlomai, P Hung, K-I Arai, N Arai
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PYNOD, a novel Apaf-1/CED4-like protein is an inhibitor of ASC and caspase-1

by Yetao Wang, Mizuho Hasegawa, Ryu Imamura, Takeshi Kinoshita, Chiaki Kondo, Kenji Konaka, Takashi Suda , 1093
"... Recently, a large subfamily of nucleotide-binding and oligomerization domain-containing proteins that have an N-terminal pyrin-like domain and C-terminal leucine-rich repeats has been described. In this study, we identi®ed PYNOD, a novel member of this family that lacks the leucine-rich repeats. We ..."
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Recently, a large subfamily of nucleotide-binding and oligomerization domain-containing proteins that have an N-terminal pyrin-like domain and C-terminal leucine-rich repeats has been described. In this study, we identi®ed PYNOD, a novel member of this family that lacks the leucine-rich repeats. We found that human PYNOD mRNA is expressed in various tissues and at high levels in heart, skeletal muscle and brain. It is also expressed in various cell lines, including haematopoietic cell lines. PYNOD oligomerizes and binds to ASC, an adaptor protein that plays a role in apoptotic and in¯ammatory signal transduction, and to caspase-1 and IL-1b. PYNOD inhibits apoptosis-associated speck-like protein containing a CARD (ASC)-mediated NF-kB activation and apoptosis, and caspase-1-mediated IL-1b maturation, and it does so in the presence and absence of constitutively active mutants of CARD12 and PYPAF1, which are enhancers of these processes. Thus, PYNOD is a novel regulator of apoptosis and in¯ammation.

Physical interactions between Ets and NF-kB/NFAT proteins play an important role in their cooperative activation of the human immunodeficiency virus enhancer in T cells

by A G Bassuk, R T An, J M Leiden, Alexander G. Bassuk, Roshani T. Anandappa, Jeffrey, M. Leiden - J , 1997
"... cells. human immunodeficiency virus enhancer in T role in their cooperative activation of the NF-kappaB/NFAT proteins play an important Physical interactions between Ets and ..."
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cells. human immunodeficiency virus enhancer in T role in their cooperative activation of the NF-kappaB/NFAT proteins play an important Physical interactions between Ets and
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...ing sites have also been identified in the regulatory elements of several inducible lymphoid genes, including those for interleukin-3 (IL-3) (18, 19), granulocyte-macrophage colony-stimulating factor =-=(18, 66, 87, 101)-=-, IL-2 (15, 41, 42, 79, 80, 87), and IL-2 receptor alpha (44, 54, 95). Thus, this array of nuclear protein binding sites may reflect a conserved mechanism for regulating inducible lymphoid gene expres...

Blockade of T-Cell Activation by Dithiocarbamates Involves Novel Mechanisms of Inhibition of Nuclear Factor of

by Activated T Cells, Pablo Gómez Del Arco, Angel Luis Armesilla, Jose ́ Aramburu, Chun Luo, Anjana Rao, Juan Miguel Redondo , 1997
"... Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kB inhibitors have been suggested as potential therapeutic drugs ..."
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Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indi-cated that pyrrolidine DTC (PDTC) prevented NF-kB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3–T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling

Regulates the Human Interleukin-5 Gene Promoter

by unknown authors , 1995
"... Interleukin-5 (IL-5) is produced by T lymphocytes and known to support B-cell growth and eosinophilic differentiation of the progenitor cells. Using ATL-16T cells which express IL-5 mRNA, we have identified a region within the human IL-5 gene promoter that regulates IL-5 gene transcription. This cis ..."
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Interleukin-5 (IL-5) is produced by T lymphocytes and known to support B-cell growth and eosinophilic differentiation of the progenitor cells. Using ATL-16T cells which express IL-5 mRNA, we have identified a region within the human IL-5 gene promoter that regulates IL-5 gene transcription. This cis-acting sequence contains the core binding motif, (A/T)GATA(A/G), for GATA-binding family proteins and thus suggests the involvement of this family members. In this report, we describe the cloning of human GATA-4 (hGATA-4) and show that hGATA-4 selectively interacts with the 270 GATA site within the IL-5 proximal promoter region. By promoter deletion and mutation analyses, we established this region as a positive regulatory element. Co-transfection experiments revealed that both hGATA-4 and phorbol-12-myristate-13-acetate (PMA)-A23187 stimulation are necessary for IL-5 promoter activation. The requirement for another regulatory element called CLE0, which lies downstream of the 270 GATA site, was also demonstrated. ATL-16T cells express mRNAs of three GATA-binding proteins, hGATA-2, hGATA-3, and hGATA-4, and each of them has a potential to bind to the consensus (A/T)GATA(G/A) motif. However, using ATL-16T nuclear extract, we demonstrated that GATA-4 is the only GATA-binding protein that forms a specific DNA-protein complex with the 270 GATA site. An electrophoretic mobility shift assay with extracts of COS cells expressing GATA-binding proteins showed that GATA-4 has the highest binding affinity for the270 GATA site among the three GATA-binding proteins. When
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...5 promoter region, which is highly conserved among the 59 upstream regions of several cytokine genes such as the IL-3, IL-4, GM-CSF, granulocyte colony-stimulating factor (GCSF), and mouse IL-5 genes =-=(20, 23, 24)-=-. This element is known to mediate response to the T-cell activation signal that is mimicked by treatment with phorbol-12-myristate-13-acetate (PMA) and calcium ionophore (A23187) (20, 23). Although t...

© 1999 The Japanese Society for Immunology Specific regulation of Fos family

by Fei Chen, Dan Chen, Ellen V. Rothenberg
"... transcription factors in thymocytes at two developmental checkpoints ..."
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transcription factors in thymocytes at two developmental checkpoints

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by Nfatx Calcineurin, Jie Liu, Ken-ichi Arai, Naoko Arai, Email Alerts , 2013
"... This article cites 53 articles, 5 of which you can access for free at: ..."
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This article cites 53 articles, 5 of which you can access for free at:

References Subscriptions Permissions Email Alerts Suppression of Granulocyte-Macrophage Colony-Stimulating Factor Expression by Glucocorticoids Involves Inhibition of Enhancer Function by the Glucocorticoid Receptor Binding to Composite NF-AT/Activator Pr

by Philip J. Smith, David J. Cousins, Young-koo Jee, Z. Staynov, Tak H. Lee, Paul Lavender, J Immunol, Paul Lavender , 2013
"... This article cites 73 articles, 37 of which you can access for free at: ..."
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This article cites 73 articles, 37 of which you can access for free at:
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...his cytokine. This mechanism may be relevant to glucocorticoid action in asthma. Initial analysis of the GM-CSF proximal promoter, which mediates activation by known GR targets such as AP-1 and NF-�B =-=(15, 18)-=-, demonstrated that this region was insensitive to steroid. The interaction between the GR and AP-1 components is complex and does not always result in a negative effect on transcription. The effect o...

References Subscriptions Permissions Email Alerts Effect of Redox Modulation on Xenogeneic Target Cells: The Combination of Nitric Oxide and Thiol Deprivation Protects Porcine

by Endothelial Cells From Lysis, Il--activated Human, Nk Cells, Shigeru Tsuyuki, Judith A. Horvath-arcidiacono, Eda T, Shigeru Tsuyuki, Judith A. Horvath-arcidiacono, Eda T. Bloom , 2013
"... This article cites 76 articles, 31 of which you can access for free at: ..."
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This article cites 76 articles, 31 of which you can access for free at:
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...which NFAT binds as a complex with AP-1 (Fos-Jun) proteins (reviewed in Ref. 3). Among the genes described to be regulated by NFAT in T cells are IL-2 (6, 7), IL-3 (8), IL-4 (9–11), IL-5 (12), GM-CSF =-=(13, 14)-=-, IFN-� (15, 16), TNF-� (17, 18), IL-13 (19), Fas ligand (FasL) 3 (20), and CD40 ligand (21). Gene transcription by the NFAT proteins NFAT1, -2, -3, and -4 is continuously controlled by the calcium-re...

Activation and a Later Phase of Deactivation of the Transcription Factor NFAT1

by C Loh, J A Carew, J Kim, P G Hogan, A Rao, Mol Cell Biol, Christine Loh, Josephine A. Carew, Jaime Kim, Patrick G. Hogan, Anjana Rao , 1995
"... T-cell receptor stimulation elicits an early phase of activation and a later phase of deactivation of the transcription factor NFAT1. ..."
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T-cell receptor stimulation elicits an early phase of activation and a later phase of deactivation of the transcription factor NFAT1.
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...inding sites for NFAT family proteins, including those encoding the cytokines interleukin-2 (IL-2), IL-3, IL-4, IL-5, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor alpha =-=(8, 10, 15, 24, 32, 33, 44, 49, 54, 56)-=- and the cell surface receptor CD40L (53). Four NFAT family proteins, NFAT1 (formerly NFATp), NFATc, NFATx/NFAT4/ NFATc3, and NFAT3, which bind DNA with similar but not identical specificities, have b...

Human Granulocyte-Macrophage Colony-Stimulating Factor Enhancer Function Is Associated with Cooperative Interactions between AP-1 and NFATp/c

by Human Granulocyte-macrophage, P N Cockerill, A G Bert, F Jenkins, G R Ryan, M F Shannon, M A Vadas, Peter N. Cockerill, Andrew G. Bert, Fay Jenkins, Gregory R. Ryan, M. Frances Shannon, Mathew, A. Vadas , 1994
"... colony-stimulating factor enhancer function is ..."
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colony-stimulating factor enhancer function is
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...ighly specific subfamily, as many NFAT sites that do not conform to the same rigidly conserved structure have now been identified. Several cytokine gene promoters have NFAT sites termed CLEO elements =-=(19, 20)-=-, in which GGAAA core sequences directly abut weak AP-1 sites, but there is no strong cooperativity in the binding of AP-1 and NFAT to these sites (unpublished observations). In the IL-4 promoter, NFA...

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