Mitogen-induced recruitment of ERK and MSK to SRE promoter complexes by ternary complex factor Elk-1

Zhang, Hongmei; Li, Li; Παπαδοπούλου, Νεκταρία; Hodgson, Glenn; Evans, Emma L.; Galbraith, Matthew D.; Dear, Mark; Vougier, StÃ©phanie; Saxton, Janice; Shaw, Peter E.

doi:10.1093/nar/gkn099

Cited by 88 publications

(78 citation statements)

References 86 publications

(103 reference statements)

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“…MSK-1 is the major kinase for histone H3 (Ser10), and knock-out mice for msk-1 show a total inhibition of cocaine-induced H3 (Ser10) phosphorylation (Brami-Cherrier et al, 2005). A logical explanation to explain the inhibitory effect of TDE on cocaine-induced H3 phosphorylation is the recent demonstration that Elk-1 is able to recruit the ERK/ MSK-1 module at the vicinity of the nucleosome located near the SRE site of c-fos and egr-1 (Zhang et al, 2008;Drobic et al, 2010). This recruitment involves a direct protein/protein interaction between activated ERKs and the DEJL domain of Elk-1.…”

Section: Discussionmentioning

confidence: 99%

“…The cDNA constructs encoding HA-tagged Elk-1 either in its wildtype (WT) or mutated version in the DEF domain (DEF) or DEJL (docking site for ERKs and JNK, LXL) regions were provided by Dr. Pete Shaw (Zhang et al, 2008). Transient transfections of HA-tagged Elk-1 plasmids were performed on primary striatal neurons using Lipofectamine 2000 (Invitrogen) according to the instructions of the manufacturer.…”

Section: Methodsmentioning

confidence: 99%

“…These data suggest that the DEF domain of Elk-1 is necessary for histone H3 phosphorylation. Besides the DEF domain, Elk-1 contains a DEJL domain that is both responsible for the docking of Elk-1 to the MAP kinases/JNK and p38 (Sharrocks et al, 2000) and necessary for the recruitment of MSK-1 at the vicinity of histone H3 (Zhang et al, 2008). We thus reasoned that the inhibitory effect of TDE on H3 phosphorylation might be reproduced by a DEJL mutation on Elk-1.…”

Section: Molecular Evidence That the Def Docking Domain Of Elk-1 Is Imentioning

confidence: 99%

See 2 more Smart Citations

Alterations of Molecular and Behavioral Responses to Cocaine by Selective Inhibition of Elk-1 Phosphorylation

Besnard¹,

Bouveyron²,

Kappès³

et al. 2011

J. Neurosci.

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Activation of the extracellular signal-regulated kinase (ERK) signaling pathway in the striatum is crucial for molecular adaptations and long-term behavioral alterations induced by cocaine. In response to cocaine, ERK controls the phosphorylation levels of both mitogen and stress-activated protein kinase 1 (MSK-1), a nuclear kinase involved in histone H3 (Ser10) and cAMP response element binding protein phosphorylation, and Elk-1, a transcription factor involved in serum response element (SRE)-driven gene regulations. We recently characterized the phenotype of msk-1 knock-out mice in response to cocaine. Herein, we wanted to address the role of Elk-1 phosphorylation in cocaine-induced molecular, morphological, and behavioral responses. We used a cell-penetrating peptide, named TAT-DEF-Elk-1 (TDE), which corresponds to the DEF docking domain of Elk-1 toward ERK and inhibits Elk-1 phosphorylation induced by ERKs without modifying ERK or MSK-1 in vitro. The peptide was injected in vivo before cocaine administration in mice. Immunocytochemical, molecular, morphological, and behavioral studies were performed. The TDE inhibited Elk-1 and H3 (Ser10) phosphorylation induced by cocaine, sparing ERK and MSK-1 activation. Consequently, TDE altered cocaine-induced regulation of genes bearing SRE site(s) in their promoters, including c-fos, zif268, ⌬FosB, and arc/arg3.1 (activity-regulated cytoskeleton-associated protein). In a chronic cocaine administration paradigm, TDE reversed cocaine-induced increase in dendritic spine density. Finally, the TDE delayed the establishment of cocaine-induced psychomotor sensitization and conditioned-place preference. We conclude that Elk-1 phosphorylation downstream from ERK is a key molecular event involved in long-term neuronal and behavioral adaptations to cocaine.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Molecular Evidence That the Def Docking Domain Of Elk-1 Is Imentioning

confidence: 99%

See 1 more Smart Citation

Alterations of Molecular and Behavioral Responses to Cocaine by Selective Inhibition of Elk-1 Phosphorylation

Besnard¹,

Bouveyron²,

Kappès³

et al. 2011

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…A classical marker for transcription initiation is phosphorylated serine-2 RNA polymerase II (pS2-CTD-RNAPolII) (Zhang et al, 2008). Therefore, to visualize EGFR and pS2-CTDRNAPolII localization, MCF10A cells were transfected with control or MUC1-1 siRNA and stimulated with 20 ng/ml EGF for 120 minutes.…”

Section: Egfr Colocalizes With Phosphorylated Rna Polymerase IImentioning

confidence: 99%

MUC1 regulates nuclear localization and function of the epidermal growth factor receptor

Bitler

Goverdhan

Schroeder

2010

Journal of Cell Science

106

109

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Alteration of protein trafficking and localization is associated with several diseases, including cystic fibrosis, breast cancer, colorectal cancer, leukemia and diabetes. Specifically, aberrant nuclear localization of the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, is a poor prognostic indicator in several epithelial carcinomas. It is now appreciated that in addition to signaling from the plasma membrane, EGFR also trafficks to the nucleus, and can directly bind the promoter regions of genes encoding cyclin D1 (CCND1) and B-Myb (MYBL2). We have previously established that loss of MUC1 in an EGFR-dependent transgenic mouse model of breast cancer correlates with the loss of cyclin D1 expression. Here, we provide evidence for a novel regulatory function of MUC1 in the trafficking and nuclear activity of EGFR. We found that MUC1 and EGFR interact in the nucleus of breast cancer cells, which promotes the accumulation of chromatin-bound EGFR. Additionally, the presence of MUC1 results in significant colocalization of EGFR and phosphorylated RNA polymerase II, indicating that MUC1 influences the association of EGFR with transcriptionally active promoter regions. Importantly, we found that the loss of MUC1 expression resulted in a decrease in the interaction between EGFR and the CCND1 promoter, which translated to a significant decrease in cyclin D1 protein expression. This data offers insights into a novel regulatory mechanism of EGFR nuclear function and could have important implications for evaluating nuclear localization in cancer.

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“…The Elk-1 TF is phosphorylated by the MAP kinases (103) and recruited by the SRF TF (104,105). The SRF factor binds gene promoters that possess the serum response elements (SREs) in order to induce immediate early (IE) genes such as c-FOS and EGR-1 (106). Interestingly, the SRF TF was predicted by the TFBM analysis while the genes EGR-1, -2, -3, -4 and FOSB appeared to be expressed in our system.…”

Section: Jak-stat/mapk Signaling Pathwaysmentioning

confidence: 99%

Pathway simulations in common oncogenic drivers of leukemic and rhabdomyosarcoma cells: A systems biology approach

et al. 2012

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Abstract. A part of current research has intensively been focused on the proliferation and metabolic processes governing biological systems. Since the advent of high throughput methodologies such as microarrays, the load of genomic data has increased geometrically and along with that the need for computational methods to interpret these data. In the present study, we investigated in vitro the common proliferation and metabolic processes, associated with common oncogenic pathways, as far as gene expression is concerned, between the T-cell acute lymphoblastic leukemia (CCRF-CEM) and the rhabdomyosarcoma (TE-671) cell lines. We present a computational approach, using cDNA microarrays, in order to identify commonalities between diverse biological systems. Our analysis predicted that JAK1, STAT1, PIAS2 and CDK4 are the driving forces in the two cell lines. This type of analysis may lead to the understanding of the common mechanisms that transform physiological cells to malignant, and may reveal a new holistic approach to understanding the dynamics of tumor onset as well as the mechanistics behind oncogenic drivers. IntroductionIt is a fact that tumors can be as diverse as the patients carrying them. Due to these differences, tumors are extremely difficult to cure, as the effects of treatments differ depending on the patient. Previously, Nicolis showed that stem cells are found in different tumor types, suggesting that they can be the etiology of tumor maintenance and growth (1). However, there is evidence that even normal, already differentiated cells can be transformed into tumorigenic ones (1). Perilongo et al also reported a case of a child manifesting five different tumor types simultaneously (2). It may be possible that stem cells originating from the same organism possess similar mutations or alterations, thus giving rise to five different tumor types. Therefore, there is a need for the investigation of common pathways between different tumor types. The discovery of similar or opposite gene expression profiles could lead us to the understanding of a common tumor origin, if such exists.A number of studies have investigated the detection of cancer germ line genes (CGGs) both in pediatric sarcomas (3) and pediatric brain tumors (4). The discovery of global antigens for tumor vaccines could become salvatory for childhood malignancies (3). Other studies have reported the common appearance of antigens in Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET) with lymphoblastic lymphoma (5). Rhabdomyosarcoma (RMS) belongs to the PNET family of tumors, which utilize embryonic genes for their progression (6). Acute lymphoblastic leukemia (ALL), which originates from the lymphoblast, also uses embryonic mechanisms for its differentiation and progression.Another point which requires attention is the regulation of genes through transcription factors (TFs). Knowledge of gene regulatory networks is considered to be of crucial importance for understanding diseases such as cancer, and may lead to new therapeutic approaches...

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Mitogen-induced recruitment of ERK and MSK to SRE promoter complexes by ternary complex factor Elk-1

Cited by 88 publications

References 86 publications

Alterations of Molecular and Behavioral Responses to Cocaine by Selective Inhibition of Elk-1 Phosphorylation

Alterations of Molecular and Behavioral Responses to Cocaine by Selective Inhibition of Elk-1 Phosphorylation

MUC1 regulates nuclear localization and function of the epidermal growth factor receptor

Pathway simulations in common oncogenic drivers of leukemic and rhabdomyosarcoma cells: A systems biology approach

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