Physical interaction between p53 and primary response gene Egr-1

Li, Jun; Grogan, Liam; Nau, Marion M.; Allegra, Carmen J.; Chu, E.; Wright, John J.

doi:10.3892/ijo.18.4.863

Cited by 44 publications

(42 citation statements)

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“…Many effects have These genes were differentially expressed in Caco-2 cells in response to quercetin exposure Values < 0 indicate downregulation, values > 0 indicate upregulation * Indicates differential expression according to SAM analysis For all genes identified as differentially expressed a P-value was calculated using a t-test a P < 0.05; b P < 0.02; c P < 0.01 These genes were differentially expressed in Caco-2 cells in response to quercetin exposure Values < 0 indicate downregulation, values > 0 indicate upregulation * Indicates differential expression according to SAM analysis For all genes identified as differentially expressed a P-value was calculated using a t-test a P < 0.05; b P < 0.02; c P < 0.01 been described for EGR1, ranging from growth stimulation to growth suppression and from anti-apoptotic to pro-apoptotic [40]. EGR1 can interact with nuclear transcription factor and tumor suppressor p53 [41]. EGR1 was downregulated by 50 µM quercetin.…”

Section: Resultsmentioning

confidence: 99%

Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer–related mechanisms in colon cancer cells in vitro

et al. 2004

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trum of possible biological actions of the bioactive compound quercetin is made using multiple gene expression analysis. Quercetin is a flavonoid that can inhibit proliferation of tumor cells and reduce the number of aberrant crypt foci, although increase of number of colon tumors was also reported. Aim of the study In order to elucidate possible mechanisms involved in its mode of action the effect of quercetin on expression of 4000 human genes in Caco-2 cells was studied and related to functional effects. Methods Caco-2 cells were exposed to 5 or 50 µM quercetin for 48 hours, differential expression of 4000 human genes was studied using microarrays and related to functional effects. Differentially expressed genes were categorized in seven functional groups: cell cycle and differentiation, apoptosis, tumor suppressor genes and oncogenes, cell adhesion and cell-cell interaction, transcription, signal transduction and energy metabolism. Also, cell proliferation and cell cycle distribution were measured. Results Quercetin (5 µM) downregulated expression of cell cycle genes (for example CDC6, CDK4 and cyclin D1), downregulated cell proliferation and induced cell cycle arrest in Caco-2 cells. After exposure to 50 µM quercetin cell proliferation decreased to 51.3 % of control, and further decrease of the percentage of cells in the G1 phase coincided with an increase of the percentage of cells in the sub-G1 phase. Quercetin upregulated expression of several tumor suppressor genes. In addition, genes involved in signal transduction pathways like beta catenin/ TCF signalling and MAPK signal transduction were influenced by quercetin. Conclusions This study shows that large-scale gene expression analysis in combination with functional assays yields a considerable amount of information on (anti-)carcinogenic potential of food components like quercetin.

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Section: Resultsmentioning

confidence: 99%

Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer–related mechanisms in colon cancer cells in vitro

et al. 2004

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“…Recent studies provide evidences that Egr-1 is also a proapoptotic protein, [37][38][39] whereas ectopic overexpression of Egr-1 sensitizes cells to undergo apoptosis. 40 Egr-1 has been designated as one of the upstream activators of NAG-1.…”

Section: Discussionmentioning

confidence: 99%

A novel anticancer effect of Astragalus saponins: Transcriptional activation of NSAID‐activated gene

Auyeung

Cho

2009

Intl Journal of Cancer

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Astragalus membranaceus has been used to ameliorate the side effects of antineoplastic drugs because of its immunomodulating nature. We had recently demonstrated that total Astragalus saponins (AST) possess anticarcinogenic and proapoptotic properties in human colon cancer cells and tumor xenograft. In this study, we identified NSAID-activated gene (NAG-1) as a potential molecular target of AST. The growth-inhibitory and proapoptotic effects of AST were assessed in a panel of human cancer cell lines. Hoechst 33342 nuclear staining, Annexin V-FITC/propidium iodide staining, Western immunoblotting, real-time PCR, luciferase reporter assay and electrophoretic mobility shift assay were conducted to determine the association of NAG-1 and related transcription factors with AST during its regulation of apoptotic activities. Moreover, the combined proapoptotic and NAG-1 promoting activities of AST and/or inhibitors of the PI3K-Akt pathway were also examined. AST caused overexpression of NAG-1, leading to PARP cleavage and apoptosis. The induction of NAG-1 promoter activity by the drug was associated with increased gene expression, in addition to prior increase in Egr-1 expression and DNA binding activity. AST-induced NAG-1 activation was intensified when PI3K inhibitor LY294002 or Akt inhibitor was cotreated and reversed by NAG-1 siRNA transfection. Nevertheless, the extent of NAG-1 induction could not be altered by the ERK inhibitor PD98059. Our results indicate that NAG-1 is a potential molecular target of AST in its antitumorigenic and proapoptotic actions, which would have additive effects when used along with PI3K-Akt inhibitors. The information obtained could facilitate future development of a novel target-specific chemotherapeutic agent with known molecular pathway. ' 2009 UICC

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“…EGR proteins form physical complexes with NF-κB proteins p65 and p50 (Fig. 1) and also with other lineage-specific nuclear factors, such as (i) NFAT proteins (NFATc and NFATp) (Decker et al, 1998;Decker et al, 2000), (ii) the homeobox protein Ptx1 and steroidogenic factor 1 (Tremblay and Droiun, 1999), (iii) the cAMP-responsive-element-binding-protein-binding protein CBP/p300 (Silverman et al, 1998), and (iv) the tumor suppressor p53 (Liu et al, 2001). In addition interaction of Journal of Cell Science 118 (14) Cooperation of EGR-4 with the nuclear mediator NF-κB EGR-1 with viral proteins like HBx (Yoo et al, 1996a), IE2 (Yoo et al, 1996b), tax (Trejo et al, 1996) and tat (Yang et al, 2002), or with NAB repressor proteins (Russo et al, 1995;Svaren et al, 1996) has been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Early growth response proteins EGR-4 and EGR-3 interact with immune inflammatory mediators NF-κB p50 and p65

Wieland

Nehmann

Müller

et al. 2005

Journal of Cell Science

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IntroductionAntigenic stimulation of T cells is induced by T-cell-receptor ligation and results in the release of immune mediators such as cytokines and chemokines. This activation initiates a nuclear program that results in activation of early growth response factors (EGRs), NF-κB, NF-AT, AP-1 and STAT proteins, and de novo transcription of the corresponding genes. In general terms, these immediate-early genes encode DNA-binding transcription factors. Following transcription, protein expression and nuclear translocation, these effector proteins bind to their cognate promoters and initiate transcription of cytokine, chemokine and inflammatory genes. The precise mechanism of how, in lymphocytes, individual transcription factors interact with coactivators and basal transcription factors, and how these DNA-binding proteins control transcription of inflammatory genes is currently unclear.The four EGR zinc-finger transcription factors (EGR-1 to EGR-4) are transiently and coordinately induced in T cells upon antigenic stimulation and the individual proteins regulate expression of genes encoding immune effectors like interleukin 2 (IL-2) (Skerka et al., 1995), tumor necrosis factor α (TNF-α) (Krämer et al., 1994), the β chain of the IL-2 receptor (Lin and Leonard, 1997), Fas (Dinkel et al., 1997) and the Fas ligand (Li-Weber et al., 1999). In addition, EGR proteins are expressed in distinct cell types and regulate transcription of a wide range of genes, including genes involved in the control of cell growth and apoptosis (Gashler and Sukhatme, 1995).There is a large panel of EGR-regulated genes and these target genes show tissue-specific expression (Gashler and Sukhatme, 1995). The restricted expression pattern of the target genes contrasts with the ubiquitous expression of EGR proteins and it is hypothesized that the tissue-specific transcription is mediated by additional nuclear proteins that cooperate with EGR proteins. We have previously shown that, in T cells, EGR-1 and EGR-4 form stable complexes with the nuclear factor of activated T cells (NFAT) (Decker et al., 2003).NF-κB is a transcription factor that plays a key role in inflammation and the immune response. The NF-κB family has five members, including RelA (p65), RelB, c-Rel, NF-κB1 (p105-p50) and NF-κB2 (p100-p52) (Hayden and Gosh, 2004). 3203Here, we characterize the basis for the T-cell-specific activity of the human zinc-finger protein early growth response factor 4 (EGR-4). A yeast two-hybrid screen showed interaction of EGR-4 with NF-κB p50. Using recombinant proteins, stable physical complex formation was confirmed for EGR-4 and EGR-3 with p50 and with p65 using glutathione-S-transferase pull-down assays and surface-plasmon-resonance and peptide-spot analyses. In vivo interaction of EGR-4 and EGR-3 with NF-κB p65 was demonstrated by immunoprecipitation experiments and fluorescence-resonance-energy transfer (FRET) analysis showing interaction in the nucleus of transfected Jurkat T cells. In transfection assays, EGR-p50 complexes were transcriptionally...

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Physical interaction between p53 and primary response gene Egr-1

Cited by 44 publications

References 0 publications

Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer–related mechanisms in colon cancer cells in vitro

Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer–related mechanisms in colon cancer cells in vitro

A novel anticancer effect of Astragalus saponins: Transcriptional activation of NSAID‐activated gene

Early growth response proteins EGR-4 and EGR-3 interact with immune inflammatory mediators NF-κB p50 and p65

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