Opposite effects of inhibitors of mitogen-activated protein kinase pathways on the egr-1 and β-globin expression in erythropoietin-responsive murine erythroleukemia cells

Schaefer, András; Kósa, Ferenc; Bittorf, Thomas; Magócsi, Mária; Rosche, Anette; Ramirez-Chávez, Yoandra; Marotzki, Stefan; Marquardt, Hans

doi:10.1016/j.cellsig.2003.07.001

Cited by 16 publications

(22 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[27][28][29][39][40][41][42] However, only Egr1 has previously been associated with EPO action. 27,40 As a zinc finger transcription factor that is subject to extracellular regulated kinase 1/2 (ERK1/2) activation, EGR1 can itself enhance both D2 cyclin 43 and Nab2 expression. 41,44 NAB2 interestingly can then act as an EGR1 repressor, and can affect not only cell growth, but also terminal differentiation (eg, of Schwann cells).…”

Section: Resultsmentioning

confidence: 99%

“…16 Depending on the model system used, EPO also has been reported to up-modulate myelocytomatosis oncogene (Myc), FBJ osteosarcoma oncogene (Fos), and/or early growth response 1 (Erg1). [25][26][27] Therefore, several cases exist for possible EPO modulation of The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734.…”

mentioning

confidence: 99%

See 1 more Smart Citation

EPO modulation of cell-cycle regulatory genes, and cell division, in primary bone marrow erythroblasts

Fang

Menon

Kapelle

et al. 2007

Blood

View full text Add to dashboard Cite

Erythropoietin (EPO's) actions on erythroblasts are ascribed largely to survival effects. Certain studies, however, point to EPO-regulated proliferation. To investigate this problem in a primary system, Kit pos CD71 high erythroblasts were prepared from murine bone marrow, and were first used in the array-based discovery of EPO-modulated cell-cycle regulators. Five cell-cycle progression factors were rapidly up-modulated: nuclear protein 1 (Nupr1), G1 to S phase transition 1 (Gspt1), early growth response 1 (Egr1), Ngfi-A binding protein 2 (Nab2), and cyclin D2. In contrast, inhibitory cyclin G2, p27/Cdkn1b, and B-cell leukemia/ lymphoma 6 (Bcl6) were sharply downmodulated. For CYCLIN G2, ectopic expression also proved to selectively attenuate EPO-dependent UT7epo cellcycle progression at S-phase. As analyzed in primary erythroblasts expressing minimal EPO receptor alleles, EPO repression of cyclin G2 and Bcl6, and induction of cyclin D2, were determined to depend on PY343 ( IntroductionThrough gene disruption experiments, 1 erythropoietin (EPO) and its dimeric single transmembrane receptor (EPOR) are known to be essential for erythroblast formation beyond a colony-forming unit-erythroid stage. In these erythroid progenitor cells, the EPOR plays a key survival role 2,3 and couples EPO to several antiapoptotic pathways. These include EPOR PY479 coupling to p85alpha PI3-kinase, thymoma viral proto-oncogene 1 (AKT), mammalian target of rapamycin (mTOR), and forkhead box O3a (FOXO3A) signal transduction factors. [4][5][6] A constitutively active AKT mutant also can rescue Janus kinase 2 (JAK2)-deficient fetal liver erythroblast development, 7 and ectopically expressed Bcl-2-like-1 (BCL-XL) can support erythroblast formation in the absence of Stat5 and/or EPO signaling. 8 In addition, an EPOR PY343 Stat5 binding site may promote Bcl-xl gene expression, 9,10 and recently this cytoplasmic phosphotyrosine site (and associated transduction pathways) have been shown to support stress erythropoiesis. 11 Erythroid progenitor cells are also sharply regulated within the contexts of both renewal and differentiation divisions. 12 Differentiation divisions occur during late-stage development, and exhibit a shortened G1-phase. 13 In such differentiating erythroblasts, E2F transcription factor 4 (E2F4) interestingly has been shown to selectively promote proliferation, and to possibly regulate several cell-cycle-associated genes (eg, Cyclin A2 [Ccna2], minichromosome maintenance deficient 2 mitotin (Mcm2) and proviral insertion Emi 1 [Emi1]). 14,15 E2F4-deficient peripheral erythrocytes also are macrocytic, implicating E2F4 effects on size control. Renewal erythroid divisions, in contrast, exhibit more standard cell-cycle properties, and are stimulated during hypoxic stress and anemia. 12 The nature of factors that exert primary control over erythroid progenitor renewal divisions, however, is less clear.Several previous studies (predominantly in cell line models) have suggested that EPO also may modulate erythroid progenitor proli...

show abstract

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

EPO modulation of cell-cycle regulatory genes, and cell division, in primary bone marrow erythroblasts

Fang

Menon

Kapelle

et al. 2007

Blood

View full text Add to dashboard Cite

show abstract

“…31 The induction of Egr-1 correlated with suppression of ␤-globin mRNA expression in Epo-responsive murine erythroblast cell line. 30 Moreover, EGR1 is up-regulated in sickle cell disease in response to hydroxyurea. 32 EGR1 may play a role in hemoglobin switching by competing with EKLF and suppressing ␤-globin expression.…”

Section: Discussionmentioning

confidence: 99%

Cytokine-mediated increases in fetal hemoglobin are associated with globin gene histone modification and transcription factor reprogramming

Sripichai

Kiefer

Bhanu

et al. 2009

Blood

View full text Add to dashboard Cite

Therapeutic regulation of globin genes is a primary goal of translational research aimed toward hemoglobinopathies. Signal transduction was used to identify chromatin modifications and transcription factor expression patterns that are associated with globin gene regulation. Histone modification and transcriptome profiling were performed using adult primary CD34 ؉ cells cultured with cytokine combinations that produced low versus high levels of gamma-globin mRNA and fetal hemoglobin (HbF). Embryonic, fetal,

show abstract

“…Others and we have previously demonstrated that curcumin effectively inhibits the ERK activity in a Curcumin suppresses expression of egfr A Chen et al variety of cells, including colon cancer cells (Chen and Tan, 1998;Chen et al, 1999;Jobin et al, 1999). Curcumin inhibition of gene expression of Egr-1 requires interruption of the ERK signal pathway (Fujita et al, 2004;Harja et al, 2004;Schaefer et al, 2004). egr-1 promoter deletion analyses and gel shift assays identified a cis-activating element (nucleotides À376 to À350) binding to the transcription factor Elk-1 (Chen et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1

2005

View full text Add to dashboard Cite

High expression of epidermal growth factor receptor (EGFR) is found in a variety of solid tumors, including colorectal cancer. EGFR has been identified as a rational target for anticancer therapy. Curcumin, the yellow pigment of turmeric in curry, has received attention as a promising dietary supplement for cancer prevention and treatment. We recently reported that curcumin inhibited the growth of human colon cancer-derived Moser cells by suppressing gene expression of cyclinD1 and EGFR. The aim of the present study was to explore the molecular mechanisms underlying curcumin inhibition of gene expression of EGFR in colon cancer cells. The generality of the inhibitory effect of curcumin on gene expression of EGFR was verified in other human colon cancer-derived cell lines, including Caco-2 and HT-29 cells. Promoter deletion assays and sitedirected mutageneses identified a binding site for the transcription factor early growth response-1 (Egr-1) in egfr promoter as a putative curcumin response element in regulating the promoter activity of the gene in Moser cells. Electrophoretic mobility shift assays demonstrated that curcumin significantly reduced the DNA-binding activity of the transcription factor Egr-1 to the curcumin response element. In addition, curcumin reduced the trans-activation activity of Egr-1 by suppressing egr-1 gene expression, which required interruption of the ERK signal pathway and reduction of the level of phosphorylation of Elk-1 and its activity. Taken together, our results demonstrated that curcumin inhibited human colon cancer cell growth by suppressing gene expression of EGFR through reducing the trans-activation activity of Egr-1. These results provided novel insights into the mechanisms of curcumin inhibition of colon cancer cell growth and potential therapeutic strategies for treatment of colon cancer.

show abstract

Opposite effects of inhibitors of mitogen-activated protein kinase pathways on the egr-1 and β-globin expression in erythropoietin-responsive murine erythroleukemia cells

Cited by 16 publications

References 64 publications

EPO modulation of cell-cycle regulatory genes, and cell division, in primary bone marrow erythroblasts

EPO modulation of cell-cycle regulatory genes, and cell division, in primary bone marrow erythroblasts

Cytokine-mediated increases in fetal hemoglobin are associated with globin gene histone modification and transcription factor reprogramming

Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1

Contact Info

Product

Resources

About