Stabilization of Interleukin-2 mRNA by the c-Jun NH
            <sub>2</sub>
            -Terminal Kinase Pathway

Chen, Ching-Yi; Gatto–Konczak, Fabienne Del; Wu, Zhenguo; Karin, Michael

doi:10.1126/science.280.5371.1945

Cited by 333 publications

(284 citation statements)

References 21 publications

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“…This phenomenon is mediated through speci®c elements in the 5' and 3' UTRs for IL2 and 3' UTR for IL3 (Chen et al, 1998;Ming et al, 1998). While the nature of JNK role in this stabilization is to be determined, the JNK-dependency points to a clear relationship between ROS and the stabilization of these mRNAs.…”

Section: Redox E Ect On Mrna Stabilitymentioning

confidence: 99%

Role of redox potential and reactive oxygen species in stress signaling

et al. 1999

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Stress-activated signaling cascades are a ected by altered redox potential. Key contributors to altered redox potential are reactive oxygen species (ROS) which are formed, in most cases, by exogenous genotoxic agents including irradiation, in¯ammatory cytokines and chemical carcinogens. ROS and altered redox potential can be considered as the primary intracellular changes which regulate protein kinases, thereby serving as an important cellular component linking external stimuli with signal transduction in stress response. The mechanisms, which underlie the ROS-mediated response, involve direct alteration of kinases and transcription factors, and indirect modulation of cysteine-rich redox-sensitive proteins exempli®ed by thioredoxin and glutathione Stransferase. This review summarizes the current understanding of the mechanisms contributing to ROS-related changes in key stress activated signaling cascades.

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Section: Redox E Ect On Mrna Stabilitymentioning

confidence: 99%

Role of redox potential and reactive oxygen species in stress signaling

et al. 1999

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“…Cyclosporine A rapidly inhibits NFAT-dependent IL-2 transcription without affecting IL-2 mRNA stability (12)(13)(14). Total RNA was isolated using TRIzol (Invitrogen Life Technologies), and the level of IL-2 mRNA was determined by normalization to a T cell-specific gene, CD3␦, using the ⌬⌬C T method for relative quantitation with IL-2 mRNA levels in the absence of Ag as the calibrator.…”

Section: Real Time Rt-pcrmentioning

confidence: 99%

Cutting Edge: CD28-Mediated Transcriptional and Posttranscriptional Regulation of IL-2 Expression Are Controlled through Different Signaling Pathways

Sánchez-Lockhart

Marin

Graf

et al. 2004

The Journal of Immunology

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Despite the clear functional importance of CD28 costimulation, the signaling pathways transduced through CD28 have remained controversial. PI3K was identified early as a candidate for CD28 signaling, but conflicting data during the past decade has left the role of PI3K unresolved. In this report, we have resolved this controversy. We show that mutation of the PI3K interaction site in the cytosolic tail of CD28 site disrupts the ability of CD28 to recruit protein kinase C-θ to the central supramolecular activation cluster (c-SMAC) region of the immunological synapse, promote NF-κB nuclear translocation, and enhance IL-2 gene transcription. In contrast, mutation of the PI3K interaction site had no effect on the ability of CD28 to enhance IL-2 mRNA stability. These results suggest that two distinct pathways mediate CD28-induced up-regulation of IL-2 expression, a PI3K-dependent pathway that may function through the immunological synapse to enhance IL-2 transcription and a PI3K-independent pathway that induces IL-2 mRNA stability.

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“…LPS activation may occur via a calcium-independent PKC (⑀ or ␦) and require inducible transcriptional mediators, possibly AP-1. c-Jun can also influence mRNA stability (43) and its involvement in enhancing stability of LPS-induced transcripts is worthy of testing. On the other hand, the response induced by IFN may be mediated by Ca 2ϩ -dependent PLC to generate PKC and activate MAPK.…”

Section: Figurementioning

confidence: 99%

IFN-γ and TNF Regulate Macrophage Expression of the Chemotactic S100 Protein S100A8

Geczy

2000

The Journal of Immunology

113

111

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The murine calcium-binding protein S100A8 is a potent chemoattractant for neutrophils and monocytes in vivo and in vitro but may also play a protective role. We show that the kinetics of induction of S100A8 mRNA in elicited murine macrophages (Mac) by LPS, IFN-γ, and TNF were distinct from the C-C chemokines monocyte chemoattractant protein-1 (MCP-1), macrophage-inflammatory protein-1α (MIP-1α), and RANTES. Monomeric S100A8 was predominantly secreted. IFN substantially increased S100A8 mRNA levels after 1 h with optimal induction after 12 h; induction by TNF was slower and more sustained. TNF did not up-regulate MCP-1 and MIP-1α mRNA in these cells. Luciferase reporter assays confirmed that LPS and IFN induce S100A8 gene transcription and mRNA in LPS-treated Mac showed little decay over 16 h, whereas transcripts induced by IFN and TNF were markedly less stable. Newly synthesized proteins may be required for mRNA transcription and stabilization in response to LPS. S100A9 associates with A8 in neutrophils, but was not coinduced with S100A8. S100A8 gene induction in Mac stimulated with LPS and IFN may be modulated by mobilization of intracellular Ca2+ concentration from distinct intracellular stores and/or the extracellular compartment and by distinct pathways involving protein kinase C and leading to activation of mitogen-activated protein kinase.

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Stabilization of Interleukin-2 mRNA by the c-Jun NH ₂ -Terminal Kinase Pathway

Cited by 333 publications

References 21 publications

Role of redox potential and reactive oxygen species in stress signaling

Role of redox potential and reactive oxygen species in stress signaling

Cutting Edge: CD28-Mediated Transcriptional and Posttranscriptional Regulation of IL-2 Expression Are Controlled through Different Signaling Pathways

IFN-γ and TNF Regulate Macrophage Expression of the Chemotactic S100 Protein S100A8

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Stabilization of Interleukin-2 mRNA by the c-Jun NH 2 -Terminal Kinase Pathway

Cited by 333 publications

References 21 publications

Role of redox potential and reactive oxygen species in stress signaling

Role of redox potential and reactive oxygen species in stress signaling

Cutting Edge: CD28-Mediated Transcriptional and Posttranscriptional Regulation of IL-2 Expression Are Controlled through Different Signaling Pathways

IFN-γ and TNF Regulate Macrophage Expression of the Chemotactic S100 Protein S100A8

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Stabilization of Interleukin-2 mRNA by the c-Jun NH ₂ -Terminal Kinase Pathway