Extranuclear effects of estrogen on cortical bone in males is dependent on estrogen receptor A activation function-1

2016 ◽  
Author(s):  
Helen Farman ◽  
Jianyao Wu ◽  
Karin Gustafsson ◽  
Sara Windahl ◽  
Sung Kim ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cortical Bone ◽  
Activation Function

Mice lacking estrogen receptor [alpha] in hypothalamic POMC neurons display enhanced estrogenic response on cortical bone mass

2016 ◽  
Author(s):  
Helen Farman ◽  
Sara Windahl ◽  
Deborah Clegg ◽  
Shang Kui Xie ◽  
Lars Westberg ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bone Mass ◽  
Cortical Bone ◽  
Estrogen Receptor Alpha ◽  
Receptor Alpha ◽  
Cortical Bone Mass

scholarly journals Rapid Estrogen-Induced Phosphorylation of the SRC-3 Coactivator Occurs in an Extranuclear Complex Containing Estrogen Receptor

2005 ◽  
Vol 25 (18) ◽  
pp. 8273-8284 ◽  
Author(s):  
Fuzhong F. Zheng ◽  
Ray-Chang Wu ◽  
Carolyn L. Smith ◽  
Bert W. O'Malley
Keyword(s):  
Estrogen Receptor ◽  
Ligand Binding ◽  
Direct Interaction ◽  
Activation Function ◽  
Estrogen Receptor Α ◽  
Binding Domain ◽  
Phosphorylation Sites ◽  
Binding Domains ◽  
Nongenomic Action ◽  
Binding Groove

ABSTRACT SRC-3/AIB1/ACTR/pCIP/RAC3/TRAM1 is a primary transcriptional coregulator for estrogen receptor (ER). Six SRC-3 phosphorylation sites have been identified, and these can be induced by steroids, cytokines, and growth factors, involving multiple kinase signaling pathways. Using phosphospecific antibodies for six phosphorylation sites, we investigated the mechanisms involved in estradiol (E2)-induced SRC-3 phosphorylation and found that this occurs only when either activated estrogen receptor α (ERα) or activated ERβ is present. Both the activation function 1 and the ligand binding domains of ERα are required for maximal induction. Mutations in the coactivator binding groove of the ERα ligand binding domain inhibit E2-stimulated SRC-3 phosphorylation, as do mutations in the nuclear receptor-interacting domain of SRC-3, suggesting that ERα must directly contact SRC-3 for this posttranslational modification to take place. A transcriptionally inactive ERα mutant which localizes to the cytoplasm supports E2-induced SRC-3 phosphorylation. Mutations of the ERα DNA binding domain did not block this rapid E2-dependent SRC-3 phosphorylation. Together these data demonstrate that E2-induced SRC-3 phosphorylation is dependent on a direct interaction between SRC-3 and ERα and can occur outside of the nucleus. Our results provide evidence for an early nongenomic action of ER on SRC-3 that supports the well-established downstream genomic roles of estrogen and coactivators.

scholarly journals Ligand-Independent Recruitment of SRC-1 to Estrogen Receptor β through Phosphorylation of Activation Function AF-1

1999 ◽  
Vol 3 (4) ◽  
pp. 513-519 ◽  
Author(s):  
André Tremblay ◽  
Gilles B Tremblay ◽  
Fernand Labrie ◽  
Vincent Giguère
Keyword(s):  
Estrogen Receptor ◽  
Activation Function ◽  
Estrogen Receptor Β

scholarly journals The Human Estrogen Receptor-α Isoform hERα46 Antagonizes the Proliferative Influence of hERα66 in MCF7 Breast Cancer Cells

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5474-5484 ◽  
Author(s):  
Graziella Penot ◽  
Christine Le Péron ◽  
Yohann Mérot ◽  
Eva Grimaud-Fanouillère ◽  
François Ferrière ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Estrogen Receptor ◽  
Cell Growth ◽  
Activation Function ◽  
Estrogen Receptor Α ◽  
Breast Cancer Cell Lines ◽  
Mcf7 Cells ◽  
Exact Function ◽  
Human Estrogen Receptor

The expression of two human estrogen receptor-α (hERα) isoforms has been characterized within estrogen receptor-α-positive breast cancer cell lines such as MCF7: the full-length hERα66 and the N terminally deleted hERα46, which is devoid of activation function (AF)-1. Although hERα66 is known to mediate the mitogenic effects that estrogens have on MCF7 cells, the exact function of hERα46 in these cells remains undefined. Here we show that, during MCF7 cell growth, hERα46 is mainly expressed in the nucleus at relatively low levels, whereas hERα66 accumulates in the nucleus. When cells reach confluence, the situation reverses, with hERα46 accumulating within the nucleus. Although hERα46 expression remains rather stable during an estrogen-induced cell cycle, its overexpression in proliferating MCF7 cells provokes a cell-cycle arrest in G0/G1 phases. To gain further details on the influence of hERα46 on cell growth, we used PC12 estrogen receptor-α-negative cell line, in which stable transfection of hERα66 but not hERα46 allows estrogens to behave as mitogens. We next demonstrate that, in MCF7 cells, overexpression of hERα46 inhibits the hERα66-mediated estrogenic induction of all AF-1-sensitive reporters: c-fos and cyclin D1 as well as estrogen-responsive element-driven reporters. Our data indicate that this inhibition occurs likely through functional competitions between both isoforms. In summary, hERα46 antagonizes the proliferative action of hERα66 in MCF7 cells in part by inhibiting hERα66 AF-1 activity.

scholarly journals Binding of Estrogen Receptor β to Estrogen Response Element in Situ Is Independent of Estradiol and Impaired by Its Amino Terminus

2005 ◽  
Vol 19 (11) ◽  
pp. 2696-2712 ◽  
Author(s):  
Jing Huang ◽  
Xiaodong Li ◽  
Casey A. Maguire ◽  
Russell Hilf ◽  
Robert A. Bambara ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Activation Function ◽  
Amino Terminus ◽  
Estrogen Response Element ◽  
Response Element ◽  
Estrogen Response ◽  
17Β Estradiol ◽  
Additional Explanation

Abstract The functions of 17β-estradiol (E2) are mediated by estrogen receptor (ER) α and β. ERs display similar DNA- and ligand-binding properties in vitro. However, ERβ shows lower transcriptional activity than ERα from the estrogen response element (ERE)-dependent signaling. We predicted that distinct amino termini contribute to differences in transcription efficacies of ERs by affecting in situ ER-ERE interactions. We used chromatin immunoprecipitation and a novel in situ ERE competition assay, which is based on the ability of ER to compete for ERE binding with a designer activator that constitutively induces transcription from an ERE-driven reporter construct. Interference of activator-mediated transcription by unliganded or liganded ERs was taken as an indication of ER-ERE interaction. Results revealed that ERs interacted with ERE similarly in the absence of E2. However, E2 enhanced the ERE binding of ERα but not that of ERβ. The removal of the amino terminus increased the ERβ-ERE interaction independent of E2. The ERβ amino terminus also prevented E2-mediated enhancement of the chimeric ERα-ERE interaction. Thus, the amino terminus of ERβ impairs the binding of ERβ to ERE. The abrogation of ligand-dependent activation function 2 of the amino-terminally truncated ERβ resulted in the manifestation of E2 effect on ERβ-ERE interaction. This implies that E2-mediated enhancement of ERβ-ERE interaction is masked by the activation function 2, whereas the intact amino terminus is a dominant region that decreases the binding of ERβ to ERE. Thus, ERβ-ERE interaction is independent of E2 and is impaired by its amino terminus. These findings provide an additional explanation for differences between ERα and ERβ functions that could differentially affect the physiology and pathophysiology of E2 signaling.

N-Terminal Activation Function Is Dominant in Ligand-Dependent Transactivation of Medaka Estrogen Receptor α in Human Cells

2001 ◽  
Vol 289 (3) ◽  
pp. 763-768 ◽  
Author(s):  
Yoshihiro Mezaki ◽  
Tasuku Yoshida ◽  
Junn Yanagisawa ◽  
Shigeaki Kato
Keyword(s):  
Estrogen Receptor ◽  
Activation Function ◽  
Estrogen Receptor Α ◽  
Human Cells

scholarly journals Antagonist-Induced, Activation Function-2-Independent Estrogen Receptor α Phosphorylation

2006 ◽  
Vol 20 (3) ◽  
pp. 516-533 ◽  
Author(s):  
Lorraine Lipfert ◽  
John E. Fisher ◽  
Nan Wei ◽  
Angela Scafonas ◽  
Qin Su ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Activation Function ◽  
Estrogen Receptor Α
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