scholarly journals Cloning and Expression of a Novel Dominant-Negative-acting Estrogen Response Element-binding Protein in the Heterogeneous Nuclear Ribonucleoprotein Family

1998 ◽  
Vol 273 (47) ◽  
pp. 31352-31357 ◽  
Author(s):  
Hong Chen ◽  
Bing Hu ◽  
Mercedes A. Gacad ◽  
John S. Adams
Keyword(s):  
Binding Protein ◽  
Dominant Negative ◽  
Cloning And Expression ◽  
Estrogen Response Element ◽  
Response Element ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Estrogen Response ◽  
Element Binding Protein ◽  
Nuclear Ribonucleoprotein

scholarly journals Creation of Estrogen Resistance in Vivo by Transgenic Overexpression of the Heterogeneous Nuclear Ribonucleoprotein-Related Estrogen Response Element Binding Protein

Endocrinology ◽  
2005 ◽  
Vol 146 (10) ◽  
pp. 4266-4273 ◽  
Author(s):  
Hong Chen ◽  
William Stuart ◽  
Bing Hu ◽  
Lisa Nguyen ◽  
Ganghua Huang ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Binding Protein ◽  
Primate Species ◽  
Target Cells ◽  
Estrogen Response Element ◽  
Response Element ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Estrogen Response ◽  
Nuclear Ribonucleoprotein

Estrogen unresponsiveness among primate species can result from overexpression of a heterogeneous nuclear ribonucleoprotein (hnRNP) that competes with estrogen receptor (ER) for binding to the estrogen-response element (ERE). This hnRNP has been coined the “ERE-binding protein” (ERE-BP). The ERE-BP is a member of the hnRNP C-like subfamily of hnRNPs, traditionally considered to be single-strand RNA binding proteins designed for the stabilization and handling of pre-mRNA. To verify in vivo the dominant-negative actions of the ERE-BP to inhibit ER-ERE-directed transactivation and to avoid the potential for lethality from global overexpression of an hnRNP, we generated transgenic mice that overexpressed ERE-BP in breast tissue under the control of a whey acidic protein gene promoter. Graded overexpression of ERE-BP in transgenic mice was established. Founders were viable and fertile. Female transgenics in all lines gave birth to pups, but their ability to nurse was dependent on the level of ERE-BP expression in breast; high-ERE-BP expressors were unable to lactate. A gradient of impaired breast pheno(histo)type, from near normal to failed ductal development and lactational capacity, correlated with the relative level of transgene expression. ERE-BP, expressed either endogenously as a transgene or after transfection, colocalized with ERα in the nucleus of target cells. This work confirms that tissue-targeted overexpression of the ERE-BP can effectively block estrogen-ERα-ERE-directed action in vivo.

scholarly journals A new regulator of osteoclastogenesis: Estrogen response element-binding protein in bone

2011 ◽  
Vol 26 (10) ◽  
pp. 2537-2547 ◽  
Author(s):  
Hong Chen ◽  
Linda C Gilbert ◽  
X Lu ◽  
Zhaofan Liu ◽  
Shaojin You ◽  
...  
Keyword(s):  
Binding Protein ◽  
Estrogen Response Element ◽  
Response Element ◽  
Estrogen Response ◽  
Element Binding Protein

scholarly journals Control of Estradiol-Directed Gene Transactivation by an Intracellular Estrogen-Binding Protein and an Estrogen Response Element-Binding Protein

2008 ◽  
Vol 22 (3) ◽  
pp. 559-569 ◽  
Author(s):  
Hong Chen ◽  
Martin Hewison ◽  
John S. Adams
Keyword(s):  
New World ◽  
Binding Protein ◽  
Estrogen Receptor Α ◽  
Estrogen Signaling ◽  
Estrogen Response Element ◽  
New World Primates ◽  
Response Element ◽  
Estrogen Response ◽  
Element Binding Protein ◽  
Mcf 7

Abstract New World primates exhibit a form of resistance to estrogens that is associated with overexpression of an estrogen response element (ERE)-binding protein (ERE-BP) and an intracellular estradiol (E2)-binding protein (IEBP). Both proteins suppress E2-mediated transcription when overexpressed in estrogen receptor-α (ERα)-positive cells. Although ERE-BP acts as a competitor for ERE occupancy by liganded ERα, the function of IEBP and its human homolog, heat-shock protein 27 (hsp27), is less clear. In data presented here, we have used E2-responsive human MCF-7 breast cancer cells to show that IEBP/hsp27 can regulate estrogen signaling as a cytosolic decoy for E2 and as a protein chaperone for ERα. Furthermore, co-immunoprecipitation, colocalization, yeast two-hybrid, and glutathione S-transferase pull-down analyses indicate that IEBP/hsp27 also interacts with ERE-BP to form a dynamic complex that appears to cycle between the cytoplasm and nucleus during normal estrogen signaling. Overexpression of either IEBP/hsp27 or ERE-BP in MCF-7 cells resulted in abnormal subcellular distribution of the IEBP/hsp27 and ERE-BP, with concomitant dysregulation of ERE occupancy as determined by chromatin immunoprecipitation. We hypothesize that IEBP/hsp27 and ERE-BP not only cause hormone resistance in New World primates but are also crucial to normal estrogen signaling in human cells. This appears to involve a physical association between the two proteins to form a complex that is able to interact with both E2 and ERα in cytosolic and nuclear compartments.

scholarly journals Heterogeneous Nuclear Ribonucleoprotein A3, a Novel RNA Trafficking Response Element-binding Protein

2002 ◽  
Vol 277 (20) ◽  
pp. 18010-18020 ◽  
Author(s):  
Alice S. W. Ma ◽  
Kim Moran-Jones ◽  
Jianguo Shan ◽  
Trent P. Munro ◽  
Mark J. Snee ◽  
...  
Keyword(s):  
Binding Protein ◽  
Response Element ◽  
Rna Trafficking ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Element Binding Protein ◽  
Nuclear Ribonucleoprotein

scholarly journals Heterogeneous Nuclear Ribonucleoprotein (hnRNP) E1 Binds to hnRNP A2 and Inhibits Translation of A2 Response Element mRNAs

2006 ◽  
Vol 17 (8) ◽  
pp. 3521-3533 ◽  
Author(s):  
Linda D. Kosturko ◽  
Michael J. Maggipinto ◽  
George Korza ◽  
Joo Won Lee ◽  
John H. Carson ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
In Vitro Translation ◽  
Dependent Manner ◽  
Response Element ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Nuclear Ribonucleoprotein ◽  
Hnrnp E1

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2 is a trans-acting RNA-binding protein that mediates trafficking of RNAs containing the cis-acting A2 response element (A2RE). Previous work has shown that A2RE RNAs are transported to myelin in oligodendrocytes and to dendrites in neurons. hnRNP E1 is an RNA-binding protein that regulates translation of specific mRNAs. Here, we show by yeast two-hybrid analysis, in vivo and in vitro coimmunoprecipitation, in vitro cross-linking, and fluorescence correlation spectroscopy that hnRNP E1 binds to hnRNP A2 and is recruited to A2RE RNA in an hnRNP A2-dependent manner. hnRNP E1 is colocalized with hnRNP A2 and A2RE mRNA in granules in dendrites of oligodendrocytes. Overexpression of hnRNP E1 or microinjection of exogenous hnRNP E1 in neural cells inhibits translation of A2RE mRNA, but not of non-A2RE RNA. Excess hnRNP E1 added to an in vitro translation system reduces translation efficiency of A2RE mRNA, but not of nonA2RE RNA, in an hnRNP A2-dependent manner. These results are consistent with a model where hnRNP E1 recruited to A2RE RNA granules by binding to hnRNP A2 inhibits translation of A2RE RNA during granule transport.

scholarly journals CREB (cAMP response element binding protein) and C/EBPα (CCAAT/enhancer binding protein) are required for the superstimulation of phosphoenolpyruvate carboxykinase gene transcription by adenoviral E1a and cAMP

2000 ◽  
Vol 352 (2) ◽  
pp. 335-342 ◽  
Author(s):  
John M. ROUTES ◽  
Lillester A. COLTON ◽  
Sharon RYAN ◽  
Dwight J. KLEMM
Keyword(s):  
Gene Transcription ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Binding Protein ◽  
Gene Promoter ◽  
Camp Response Element Binding ◽  
Dominant Negative ◽  
Camp Response Element ◽  
Response Element ◽  
Element Binding Protein ◽  
In Cells

In the present study, we observed superstimulated levels of cAMP-stimulated transcription from the phosphoenolpyruvate carboxykinase (PEPCK) gene promoter in cells infected with wild-type adenovirus expressing 12S and 13S E1a proteins, or in cells expressing 13S E1a alone. cAMP-stimulated transcription was inhibited in cells expressing only 12S E1a, but slightly elevated in cells expressing E1a proteins with mutations in conserved regions 1 or 2, leading us to conclude that the superstimulation was mediated by conserved region 3 of 13S E1a. E1a failed to enhance cAMP-stimulated transcription from promoters containing mutations that abolish binding by cAMP response element binding protein (CREB) or CCAAT/enhancer binding proteins (C/EBPs). This result was supported by experiments in which expression of dominant-negative CREB and/or C/EBP proteins repressed E1a- and cAMP-stimulated transcription from the PEPCK gene promoter. In reconstitution experiments using a Gal4-responsive promoter, E1a enhanced cAMP-stimulated transcription when chimaeric Gal4–CREB and Gal4–C/EBPα were co-expressed. Phosphorylation of CREB on serine-133 was stimulated in cells treated with dibutyryl cAMP, whereas phosphorylation of C/EBPα was increased by E1a expression. Our data support a model in which cAMP agonists increase CREB activity and stimulate PEPCK gene transcription, a process that is enhanced by E1a through the phosphorylation of C/EBPα.

Sign in / Sign up

Export Citation Format

Share Document