Utilization of an NF-ATp Binding Promoter Element for EGR3 Expression in T Cells but Not Fibroblasts Provides a Molecular Model for the Lymphoid Cell-Specific Effect of Cyclosporin A

Mages, Hans W.; Baag, Rima; Steiner, B; Kroczek, Richard A.

doi:10.1128/mcb.18.12.7157

Cited by 23 publications

(19 citation statements)

References 46 publications

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“…Lysates were analysed for levels of total ERK1/2, phospho-ERK1/2, total p38, phospho-p38, phospho-MSK T581 and phospho-CREB by immunoblotting. examples see [40][41][42][43][44]). In addition, nur77, nor1 and c-fos have been shown to contain functional CREbinding sites, and their transcription has been shown to be inhibited by transfection of dominant-negative CREB [12,45].…”

Section: Discussionmentioning

confidence: 99%

MSK regulate TCR‐induced CREB phosphorylation but not immediate early gene transcription

et al. 2007

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Stimulation of the T cell receptor activates the ERK1/2 and p38 mitogen-activated protein kinase (MAPK) cascades. We demonstrate that TCR stimulation also activates the mitogen-and stress-activated kinases (MSK) downstream of ERK1/2 and p38 in both a T cell line and primary peripheral T cells. MSK1/2-knockout mice were found to have normal numbers of T cells in the thymus, and development of these cells appeared unaffected. Using naive T cells and T lymphoblasts from MSK1/2-knockout mice, it was found that MSK was the kinase responsible for phosphorylation of the transcription factor CREB in response to TCR stimulation. Phosphorylation of CREB by MSK has been linked to the transcription of nur77, nor1 and c-fos downstream of MAPK signalling in various cell types. In T cells, the TCR-dependent transcription of these genes was found to require a MAPK-dependent but MSK-independent signalling pathway. Nevertheless, the number of T cells present in the spleens of MSK1/2-knockout mice and the IL-2-induced proliferation of these cells was reduced compared to wild-type mice. This correlated to a reduction in the TCR-induced up-regulation of the IL-2 receptor CD25 and a requirement for MSK in IL-2-induced CREB phosphorylation.

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Section: Discussionmentioning

confidence: 99%

MSK regulate TCR‐induced CREB phosphorylation but not immediate early gene transcription

et al. 2007

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“…5D). To determine whether one of the mechanisms involved in 15d-PGJ 2 -mediated inhibition of the egr-3 gene activation could be direct interference with the transcriptional activity of its promoter, transient transfection assays were performed in Jurkat T cells using a promoter fragment spanning nucleotides from Ϫ2952 to ϩ86 bp of the human egr-3 gene (35). As shown in Fig.…”

Section: D-pgj 2 Modulates Egr Transcription Factors Expression In mentioning

confidence: 99%

The Cyclopentenone-Type Prostaglandin 15-Deoxy-Δ12,14-Prostaglandin J2 Inhibits CD95 Ligand Gene Expression in T Lymphocytes: Interference with Promoter Activation Via Peroxisome Proliferator-Activated Receptor-γ-Independent Mechanisms

Cippitelli

Fionda

Bona

et al. 2003

The Journal of Immunology

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15-Deoxy-Δ12,14-PGJ2 (15d-PGJ2) is a cyclopentenone-type PG endowed with anti-inflammatory properties and produced by different cells, including those of the immune system. 15d-PGJ2 is a natural ligand of the peroxisome proliferator-activated receptor (PPAR)-γ nuclear receptor, but relevant PPARγ-independent actions mediated by this prostanoid have been described. Fas (APO-1/CD95) and its ligand (Fas-L) are cell surface proteins whose interaction activates apoptosis of Fas-expressing targets. In T cells, the Fas-Fas-L system regulates activation-induced cell death and has been implicated in diseases in which lymphocyte homeostasis is compromised. Moreover, several studies have described the pathogenic functions of Fas and Fas-L in vivo, particularly in the induction-progression of organ-specific autoimmune diseases. In this study we describe the effect of 15d-PGJ2 on the activation of the fas-L gene in T lymphocytes. We show that 15d-PGJ2 inhibits fas-L mRNA expression, activation-induced cell death, and fas-L promoter activity by mechanisms independent of PPARγ and mediated by its chemically reactive cyclopentenone moiety. Our data indicate that 15d-PGJ2 may repress fas-L activation by interfering with the expression and/or transcriptional activity of different transcription factors (early growth response types 3 and 1, NF-κB, AP-1, c-Myc, Nur77) whose altered balancing and transactivation may contribute for overall repression of this gene. In addition, the activation/expression of the heat shock response genes HSF-1 and HSP70 is not directly involved in the repression, and the electrophilic molecule cyclopentenone (2-cyclopenten-1-one) may reproduce the effects mediated by 15d-PGJ2. These results suggest that modulation of Fas-L by 15d-PGJ2 in T cells may represent an additional tool to consider for treatment of specific autoimmune and inflammatory disorders.

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“…The lack of FasL expression in NFAT-deficient mice further supports the role of NFAT in FasL regulation (36) (31,32). Transcriptionally active NFAT binding sites are present in the promoter of Egr, and the NFAT-mediated induction of Egr-2 and Egr-3 is essential for optimal FasL expression (36,37). In addition, NF-B and the IRF family participate in regulation of FasL gene expression during T-cell activation (22,23,30,33,34).…”

Section: Discussionmentioning

confidence: 88%

Hepatitis B Virus X Protein Induces Expression of Fas Ligand Gene through Enhancing Transcriptional Activity of Early Growth Response Factor

Yoo

Lee

2004

Journal of Biological Chemistry

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Utilization of an NF-ATp Binding Promoter Element for EGR3 Expression in T Cells but Not Fibroblasts Provides a Molecular Model for the Lymphoid Cell-Specific Effect of Cyclosporin A

Cited by 23 publications

References 46 publications

MSK regulate TCR‐induced CREB phosphorylation but not immediate early gene transcription

MSK regulate TCR‐induced CREB phosphorylation but not immediate early gene transcription

The Cyclopentenone-Type Prostaglandin 15-Deoxy-Δ12,14-Prostaglandin J2 Inhibits CD95 Ligand Gene Expression in T Lymphocytes: Interference with Promoter Activation Via Peroxisome Proliferator-Activated Receptor-γ-Independent Mechanisms

Hepatitis B Virus X Protein Induces Expression of Fas Ligand Gene through Enhancing Transcriptional Activity of Early Growth Response Factor

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