Cross-talk in signal transduction: Ras-dependent induction of cAMP-responsive transcriptional repressor ICER by nerve growth factor

Monaco, Lucía; Sassone–Corsi, Paolo

doi:10.1038/sj.onc.1201636

Cited by 39 publications

(45 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1-3). Only a few previous studies on ICER gene expression have analyzed both mRNA and protein expression (3,7,9). In most of these studies, a close correlation was observed between mRNA and protein expression except for forskolin-treated AtT20 cells (3) and, as shown in this study, in macrophages.…”

Section: Discussionmentioning

confidence: 49%

“…However, such an expression profile correlates well with the kinetics of IFN-␥-inhibited genes, such as LPL (12), with maximum decreases seen between 12 and 24 h. Several extracellular mediators have been shown to increase the intracellular ICER levels, including NGF, thyroid-stimulating factor, follicle-stimulating hormone, glucagons, noradrenaline, gastrin, and cholecystokinin (7-10, 48, 51, 92). Although most of these factors act by increasing intracellular cAMP levels, the use of pharmacological agents has shown that the action of NGF and gastrin was not mediated through this route (9,10). Similarly, the use of a range of pharmacological agents showed that the IFN-␥-induced ICER expression was not affected by inhibitors of cyclic nucleotide-dependent protein kinase, MAP kinases, Ca 2ϩ /calmodulin-dependent protein kinase, protein kinase C, and JAK2 but required activation of CK2 (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…It is also possible that, besides acting as a direct repressor of genes that are expressed constitutively at high levels and inhibited by IFN-␥, ICER may also play an important role in the transcriptional suppression of immediate early genes that have been induced transiently by this cytokine through other pathways. For example, the NGF-mediated expression of ICER has been proposed to be involved in the inhibition of c-fos gene transcription once it has been induced immediately by the mediator (9).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Interferon-γ Stimulates the Expression of the Inducible cAMP Early Repressor in Macrophages through the Activation of Casein Kinase 2

Mead

Hughes

Irvine

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Interferon-␥ (IFN-␥) is a pleiotropic cytokine that modulates the immune function, cell proliferation, apoptosis, macrophage activation, and numerous other cellular responses. These biological actions of IFN-␥ are characterized by both the activation and the inhibition of gene transcription. Unfortunately, in contrast to gene activation, the mechanisms through which the cytokine suppresses gene transcription remain largely unclear. We show here for the first time that exposure of macrophages to IFN-␥ leads to a dramatic induction in the expression of the inducible cAMP early repressor (ICER), a potent inhibitor of gene transcription. In addition, a synergistic action of IFN-␥ and calcium in the activation of ICER expression was identified. The IFN-␥-mediated activation of ICER expression was not blocked by H89, bisindoylmaleimide, SB202190, PD98059, W7, and AG490, which inhibit protein kinase A, protein kinase C, p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, calcium-calmodulin-dependent protein kinase, and Janus kinase-2, respectively. In contrast, apigenin, a selective casein kinase 2 (CK2) inhibitor, was found to inhibit response. Consistent with this finding, IFN-␥ stimulated CK2 activity and the level of phosphorylated cAMP response element-binding protein, which is known to induce ICER gene transcription, and this response was inhibited in the presence of apigenin. These studies, therefore, identify a previously uncharacterized pathway, involving the IFN-␥-mediated stimulation of CK2 activity, activation of cAMP response element-binding protein, and increased production of ICER, which may then play an important role in the inhibition of macrophage gene transcription by this cytokine.

show abstract

Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Interferon-γ Stimulates the Expression of the Inducible cAMP Early Repressor in Macrophages through the Activation of Casein Kinase 2

Mead

Hughes

Irvine

et al. 2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…However, the kinetics of stimulation are different because, as demonstrated by Monaco and Sassone-Corsi (1997), CREB phosphorylation returns to basal levels after 2 h of incubation with NGF, whereas we observe a more sustained stimulation that is still noticeable after 8 h of incubation with RA. Many actions of RA are mediated by binding of RAR-RXR heterodimers to DNA response elements.…”

Section: Discussionmentioning

confidence: 57%

Rapid Effects of Retinoic Acid on CREB and ERK Phosphorylation in Neuronal Cells

Cañón

Cosgaya

Scsucova

et al. 2004

MBoC

160

View full text Add to dashboard Cite

Retinoic acid (RA) is a potent regulator of neuronal cell differentiation. RA normally activates gene expression by binding to nuclear receptors that interact with response elements (RAREs) in regulatory regions of target genes. We show here that in PC12 cell subclones in which the retinoid causes neurite extension, RA induces a rapid and sustained phosphorylation of CREB (cyclic AMP response element binding protein), compatible with a nongenomic effect. RA also causes a rapid increase of CREB phosphorylation in primary cultures of cerebrocortical cells and of dorsal root ganglia neurons from rat embryos. RA-mediated phosphorylation of CREB leads to a direct stimulation of CREB-dependent transcriptional activity and to activation of the expression of genes such as c-fos, which do not contain RAREs but contain cAMP response elements (CREs) in their promoters. CREB is a major target of extracellular signal regulated kinase ERK1/2 signaling in neuronal cells, and we demonstrate here that RA induces an early stimulation of ERK1/2, which is required both for CREB phosphorylation and transcriptional activity. These results demonstrate that RA, by a nongenomic mechanism, stimulates signaling pathways that lead to phosphorylation of transcription factors, which in turn activate the transcription of genes involved in neuronal differentiation. INTRODUCTIONPC12 cells, cloned from a rat pheochromocytoma have been widely used for studying molecular mechanisms of neuronal differentiation. On incubation with neurotrophic factors such as nerve growth factor (NGF) these cells extend long neurites and undergo biochemical changes characteristic of mature sympathetic neurons (Segal and Greenberg, 1996). The neuron-like differentiation of PC12 cells induced by NGF involves activation of the Ras/extracellular signal-regulated kinase (ERK1/2) signaling pathway. Sustained activation of ERK1/2 permits its translocation to the nucleus, where it may modulate gene expression via the phosphorylation of transcription factors or activation of other kinases (Qiu and Green, 1991;Marshall, 1995).The nuclear transcription factor cAMP response elementbinding protein (CREB) is a major downstream target of ERK1/2 signaling that contributes to neuronal differentiation in PC12 cells (Heasley et al., 1991;Ginty et al., 1994) and to brain neuroplasticity (Impey et al., 1998bSgambato et al., 1998;Pham et al., 1999) and neuronal survival (Bonni et al., 1999;Riccio et al., 1999;Nakagawa et al., 2002). CREB binds constitutively to the specific DNA motif, 5Ј-TGACGTCA-3Ј known as CRE, and its activity is triggered by phosphorylation in Ser133 (González and Montminy, 1989). Phosphorylation of Ser133 recruits the CREB binding protein, CBP, to the initiator complex and thereby promotes transcription (Chrivia et al., 1993;Arias et al., 1994;Mayr and Montminy, 2001). CREB was initially identified as a substrate for PKA and as a mediator of cAMP-regulated gene expression, but later studies showed that CREB can be phosphorylated and activated by multiple signaling p...

show abstract

“…The isoforms function either as transcriptional repressor or activator, depending on the presence or absence of the transactivating domains (Q1 and/or Q2) (13,15,16). The second promoter is responsible for the regulation of an inducible CREM, inducible cAMP earlyexpressed in the brain (17) and has been suggested to play a role in T cells (18,19). However, CREM ␣ is bigger than ICER protein (36 vs 16 kDa), possesses a kinase inducible domain, and is regulated by promoter 1.…”

mentioning

confidence: 99%

The Cyclic Adenosine 5′-Monophosphate Response Element Modulator Suppresses IL-2 Production in Stimulated T Cells by a Chromatin-Dependent Mechanism

Tenbrock

Juang

Tolnay

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

The production of IL-2 is tightly controlled by several transcription factors that bind to the IL-2 promoter. The cAMP response element modulator (CREM) is known to form complexes with CREB and bind to the −180 site of the IL-2 promoter in anergic and in systemic lupus erythematosus T cells. In this study we show that CREM is transcriptionally induced in T cells following stimulation through CD3 and CD28, binds to the IL-2 promoter in vivo, and suppresses IL-2 production. Transfection of an antisense CREM plasmid into T cells blocked the expression and binding of CREM to the IL-2 promoter and the decrease of IL-2 production, which follows the early increase after T cell stimulation with CD3 and CD28. In addition, as assessed by chromatin immunoprecipitation experiments, antisense CREM prevented the binding of protein 300 and cAMP response element binding protein and promoted the acetylation of histones. Antisense CREM also enhanced the accessibility of the IL-2 promoter to endonucleases and prevented the condensation of chromatin in vivo. Our data suggest that upon T cell activation, CREM gradually replaces phosphorylated CREB at the −180 site of the IL-2 promoter. CREM, in turn, binds protein 300 and cAMP response element binding protein, but CREM is unable to activate its histone acetyltransferase activity, which results in condensation of chromatin and down-regulation of IL-2 production.

show abstract

Cross-talk in signal transduction: Ras-dependent induction of cAMP-responsive transcriptional repressor ICER by nerve growth factor

Cited by 39 publications

References 33 publications

Interferon-γ Stimulates the Expression of the Inducible cAMP Early Repressor in Macrophages through the Activation of Casein Kinase 2

Interferon-γ Stimulates the Expression of the Inducible cAMP Early Repressor in Macrophages through the Activation of Casein Kinase 2

Rapid Effects of Retinoic Acid on CREB and ERK Phosphorylation in Neuronal Cells

The Cyclic Adenosine 5′-Monophosphate Response Element Modulator Suppresses IL-2 Production in Stimulated T Cells by a Chromatin-Dependent Mechanism

Contact Info

Product

Resources

About