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 Estradiol and Tamoxifen Mediate Rescue of the Dominant-Negative Effects of Estrogen Response Element-Binding Protein in Vivo and in Vitro

Endocrinology ◽  
2008 ◽  
Vol 150 (5) ◽  
pp. 2429-2435 ◽  
Author(s):  
Hong Chen ◽  
Thomas L. Clemens ◽  
Martin Hewison ◽  
John S. Adams
Keyword(s):  
Estrogen Receptor ◽  
Transgenic Mice ◽  
Binding Protein ◽  
Fold Increase ◽  
Estrogen Response Element ◽  
Wild Type ◽  
Branch Number ◽  
Response Element ◽  
Estrogen Response

Biological responses to estrogens are dependent on the integrated actions of proteins, including the estrogen receptor (ER)-α, that regulate the transcription of estrogen response element (ERE)-containing target genes. We have identified a naturally occurring ERE antagonist, termed an ERE-binding protein (BP). To verify that ERE-BP can induce estradiol (E2) resistance in vivo, we generated transgenic mice that overexpress this protein in breast tissue. Female transgenic mice with high levels of ERE-BP were unable to lactate, and we hypothesized that this effect was dependent on the relative levels of ERE-BP and ERα ligand. To test this hypothesis, wild-type and ERE-BP-expressing female mice were implanted with capsules containing E2, the selective estrogen receptor modulator tamoxifen, or placebo. Histological analysis of nonlactating mammary glands showed a 4.5-fold increase in gland branch number and 3.7-fold increase in ducts in ERE-BP mice treated with E2 (7.5 mg, 21 d) compared with placebo-treated ERE-BP mice. Wild-type mice showed a 5.3-fold increase in branches and 1.4-fold increase in ducts under the same conditions. Similar results were obtained with tissue from lactating mice, in which tamoxifen also increased mammary gland branch number. Studies using ERE-BP-expressing MCF-7 breast cells showed that high doses of E2 (1000 nm) restored normal ERα-chromatin interaction in these cells, whereas tamoxifen was able to achieve this effect at a dose of 10 nm. These data highlight the importance of ERE-BP as an attenuator of normal ERα signaling in vivo and further suggest that ERE-BP is a novel target for modulation by selective estrogen receptor modulators.

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.

Scutellarin Mitigates Cancer-Induced Bone Pain by Suppressing CaMKII/CREB Pathway in Rat Models

2019 ◽  
Vol 17 (3) ◽  
pp. 249-253
Author(s):  
Liu Chenglong ◽  
Liu Haihua ◽  
Zhang Fei ◽  
Zheng Jie ◽  
Wei Fang
Keyword(s):  
Protein Kinase ◽  
Bone Pain ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Dependent Protein Kinase ◽  
Response Element ◽  
Protein Kinase Ii ◽  
Element Binding Protein ◽  
Dependent Protein

Cancer-induced bone pain is a severe and complex pain caused by metastases to bone in cancer patients. The aim of this study was to investigate the analgesic effect of scutellarin on cancer-induced bone pain in rat models by intrathecal injection of Walker 256 carcinoma cells. Mechanical allodynia was determined by paw withdrawal threshold in response to mechanical stimulus, and thermal hyperalgesia was indicated by paw withdrawal latency in response to noxious thermal stimulus. The paw withdrawal threshold and paw withdrawal latencies were significantly decreased after inoculation of tumor cells, whereas administration of scutellarin significantly attenuated tumor cell inoculation-induced mechanical and heat hyperalgesia. Tumor cell inoculation-induced tumor growth was also significantly abrogated by scutellarin. Ca2+/calmodulin-dependent protein kinase II is a multifunctional kinase with up-regulated activity in bone pain models. The activation of Ca2+/calmodulin-dependent protein kinase II triggers phosphorylation of cAMP-response element binding protein. Scutellarin significantly reduced the expression of phosphorylated-Ca2+/calmodulin-dependent protein kinase II and phosphorylated-cAMP-response element binding protein in cancer-induced bone pain rats. Collectively, our study demonstrated that scutellarin attenuated tumor cell inoculation-induced bone pain by down-regulating the expression of phosphorylated-Ca2+/calmodulin-dependent protein kinase II and phosphorylated-cAMP-response element binding protein. The suppressive effect of scutellarin on phosphorylated-Ca2+/calmodulin-dependent protein kinase II/phosphorylated-cAMP-response element binding protein activation may serve as a novel therapeutic strategy for CIBP management.

cAMP Response Element Binding Protein Is Expressed and Phosphorylated in the Human Heart

Circulation ◽  
1995 ◽  
Vol 92 (8) ◽  
pp. 2041-2043 ◽  
Author(s):  
Frank Ulrich Müller ◽  
Peter Bokník ◽  
Andreas Horst ◽  
Jörg Knapp ◽  
Bettina Linck ◽  
...  
Keyword(s):  
Human Heart ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Response Element ◽  
Element Binding Protein
Sign in / Sign up

Export Citation Format

Share Document