scholarly journals Early Growth Response Protein 1 Binds to the Luteinizing Hormone-β Promoter and Mediates Gonadotropin-Releasing Hormone-Stimulated Gene Expression

1999 ◽  
Vol 13 (5) ◽  
pp. 752-763 ◽  
Author(s):  
Michael W. Wolfe ◽  
Gerald B. Call
Keyword(s):  
Growth Response ◽  
Early Growth ◽  
Steroidogenic Factor 1 ◽  
Response Elements ◽  
Cis Acting ◽  
Early Growth Response ◽  
Endogenous Expression ◽  
Synergistic Activation

Abstract The hypothalamic neuropeptide, GnRH, regulates the synthesis and secretion of LH from pituitary gonadotropes. Furthermore, it has been shown that the LH β-subunit gene is regulated by the transcription factors steroidogenic factor-1 (SF-1) and early growth response protein 1 (Egr1) in vitro and in vivo. The present study investigated the roles played by Egr1 and SF-1 in regulating activity of the equine LHβ-subunit promoter in the gonadotrope cell line, αT3–1, and the importance of these factors and cis-acting elements in regulation of the promoter by GnRH. All four members of the Egr family were found to induce activity of the equine promoter. The region responsible for induction by Egr was localized to the proximal 185 bp of the promoter, which contained two Egr response elements. Coexpression of Egr1 and SF-1 led to a synergistic activation of the equine (e)LHβ promoter. Mutation of any of the Egr or SF-1 response elements attenuated this synergism. Endogenous expression of Egr1 in αT3–1 cells was not detectable under basal conditions, but was rapidly induced after GnRH stimulation. Reexamination of the promoter constructs harboring mutant Egr or SF-1 sites indicated that these sites were required for GnRH induction. In fact, mutation of both Egr sites within the eLHβ promoter completely attenuated its induction by GnRH. Thus, GnRH induces expression of Egr1, which subsequently activates the eLHβ promoter. Finally, GnRH not only induced expression of Egr1, but also its corepressor, NGFI-A (Egr1) binding protein (Nab1), which can repress Egr1- induced transcription of the eLHβ promoter.

scholarly journals Early Growth Response 1 Acts as a Tumor Suppressor In vivo and In vitro via Regulation of p53

2005 ◽  
Vol 65 (12) ◽  
pp. 5133-5143 ◽  
Author(s):  
Anja Krones-Herzig ◽  
Shalu Mittal ◽  
Kelly Yule ◽  
Hongyan Liang ◽  
Chris English ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Growth Response ◽  
Early Growth ◽  
Early Growth Response ◽  
Early Growth Response 1

Induction of Early Growth Response-1 Mediates Microglia Activation In Vitro But is Dispensable In Vivo

2009 ◽  
Vol 11 (2) ◽  
pp. 87-96 ◽  
Author(s):  
Thomas Langmann ◽  
Stefanie Ebert ◽  
Yana Walczak ◽  
Karin Weigelt ◽  
Markus U. Ehrengruber ◽  
...  
Keyword(s):  
Growth Response ◽  
Early Growth ◽  
Microglia Activation ◽  
Early Growth Response ◽  
Early Growth Response 1

scholarly journals Transcription Factor Early Growth Response 3 Is Associated with the TGF-β1 Expression and the Regulatory Activity of CD4-Positive T Cells In Vivo

2013 ◽  
Vol 191 (5) ◽  
pp. 2351-2359 ◽  
Author(s):  
Shuji Sumitomo ◽  
Keishi Fujio ◽  
Tomohisa Okamura ◽  
Kaoru Morita ◽  
Kazuyoshi Ishigaki ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
Growth Response ◽  
Early Growth ◽  
Regulatory Activity ◽  
Early Growth Response ◽  
Tgf Β1

scholarly journals Characterization of cis-Acting Sequences and trans-Acting Signals Regulating Early Growth Response 1 and c-fos Promoters Through the Granulocyte-Macrophage Colony-Stimulating Factor Receptor in BA/F3 Cells

Blood ◽  
1997 ◽  
Vol 89 (4) ◽  
pp. 1197-1206 ◽  
Author(s):  
Sumiko Watanabe ◽  
Hideya Kubota ◽  
Kathleen M. Sakamoto ◽  
Ken-ichi Arai
Keyword(s):  
Signaling Pathways ◽  
Growth Response ◽  
Early Growth ◽  
Β Subunit ◽  
Colony Stimulating Factor ◽  
Cis Acting ◽  
Early Growth Response ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Human granulocyte-macrophage colony-stimulating factor (hGM-CSF ) activates a set of genes such as c-fos, jun, myc, and early growth response gene 1 (egr-1). Studies on BA/F3 cells that express hGM-CSF receptor (hGMR) showed that two different signaling pathways controlled by distinct regions within the β subunit are involved in activation of c-fos/c-jun genes and in c-myc, respectively. However, the region(s) of the β subunit responsible for activation of the egr-1 gene and other regulatory genes has not been identified. We describe here how egr-1 promoter is activated by hGMR through two regions of the β subunit, with these regions being required for activation of the c-fos promoter. Coexpression of dominant negative (dn) Ras (N17ras) or dn JAK2 almost completely suppressed the activation of egr-1 and c-fos promoters. Deletion analysis of egr-1 promoter showed two cis-acting regions responsible for activation by hGM-CSF or mouse interleukin-3 (mIL-3), one between nucleotide positions (nt) −56 and −116, and the other between nt −235 and −480, which contains tandem repeats of the serum response element (SRE) sites. Similar experiments with the c-fos promoter showed that cis-acting regions containing the SRE/AP-1 sites is sufficient for activation by hGM-CSF. Based on these observations, we propose that signaling pathways activating egr-1 and c-fos promoters are controlled by SRE elements, either through the same or overlapping pathways that involve JAK2 and Ras.

Survivin Is Negatively Regulated by Early Growth Response (Egr)-1 Transcription Factor in Acute Myeloid Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1943-1943 ◽  
Author(s):  
Ingo Tamm ◽  
Karin Schmelz ◽  
Bernd Dörken ◽  
Mandy Wagner
Keyword(s):  
Transcription Factor ◽  
Cell Lines ◽  
Growth Response ◽  
Survivin Expression ◽  
Early Growth ◽  
Survivin Promoter ◽  
Over Expression ◽  
Early Growth Response ◽  
Induced Apoptosis

Abstract Survivin, a member of the inhibitor of apoptosis protein family, is involved in both, inhibition of apoptosis and regulation of cell division. It is expressed in embryonic and fetal tissues as well as in the majority of human leukemias, but is undetectable in normal differentiated adult tissue in vivo. The molecular mechanisms involved in the cancer-specific re-expression of survivin are unclear. In this study, we describe a novel mechanism for over-expression of survivin in AML. Using electrophoretic mobility shift assays (EMSA), we show that the early growth response (Egr)-1 transcription factor binds to the sequence 5′ GAGGGGGCG 3′ within the human survivin promoter after induction by phorbol 12-myristate-13-acetate (PMA) in vitro. Furthermore, chromatin immunoprecipitation (ChIP) analysis confirmed the specific binding of Egr-1 to the proximal survivin promoter in PMA treated entire leukemia cells. To further analyze the functionality of the Egr-1 site within the survivin promoter in entire cells, transient transfections of p53 wildtype and mutated cell lines with wildtype Egr-1 expression vector were performed. In these overexpression experiments, mRNA and protein levels of survivin but not of control protein were downregulated after exogenous expression of wildtype Egr-1. Using reporter-gene assays, basal survivin promoter activity was decreased significantly by wildtype Egr-1 transfection, whereas mutant Egr-1 did not change activity of the survivin promoter, implying that Egr-1 specifically blocks survivin expression at the transcriptional level. In addition, Egr-1 over-expression sensitized cells to TRAIL-induced apoptosis. To investigate the expression pattern of Egr-1 in different AML cell lines and control samples from healthy donors, we analyzed the expression of Egr-1 by RT-PCR. Fitting with the above shown data, Egr-1 was expressed at significantly lower levels in AML cell lines expressing high survivin levels than in healthy control samples with low survivin levels. Taken together, we show that the transcription factor Egr-1 binds to the human survivin promoter in vitro and in entire cells, downregulates survivin expression independently of p53 and sensitizes cells to TRAIL-induced apoptosis. Since Survivin is often overexpressed in AML, downregulating Survivin expression by activating Egr-1 may be an interesting therapeutic option.

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