Localization of an estrogen receptor binding site near the promoter of the uteroglobin gene

FEBS Letters ◽  
1990 ◽  
Vol 265 (1-2) ◽  
pp. 20-22 ◽  
Author(s):  
M.S.López de Haro ◽  
C. García ◽  
A. Nieto
Keyword(s):  
Estrogen Receptor ◽  
Binding Site ◽  
Receptor Binding ◽  
Receptor Binding Site ◽  
Estrogen Receptor Binding ◽  
Estrogen Receptor Binding Site

scholarly journals Polymorphic estrogen receptor binding site causes CD2-dependent sex bias in the susceptibility to autoimmune diseases

2021 ◽  
Author(s):  
Gonzalo Fernandez Lahore ◽  
Michael Förster ◽  
Martina Johannesson ◽  
Pierre Sabatier ◽  
Erik Lönnblom ◽  
...  
Keyword(s):  
T Cells ◽  
Estrogen Receptor ◽  
T Cell ◽  
Autoimmune Diseases ◽  
Binding Site ◽  
Receptor Binding ◽  
Receptor Binding Site ◽  
Female Mice ◽  
Estrogen Receptor Binding ◽  
Estrogen Receptor Binding Site

Abstract Complex autoimmune diseases are sexually dimorphic. An interplay between predisposing genetics and sex-related factors likely determines the sex discrepancy in the immune response, but conclusive evidence is lacking regarding the underlying molecular mechanisms. Using forward genetics, we positionally identified a polymorphic estrogen receptor binding site that regulates CD2 expression, leading to female-specific differences in mouse models of T cell-dependent autoimmunity. Female mice with reduced CD2 levels displayed diminished expansion of autoreactive T cells. Mechanistically, CD2 affected T cell activation by inhibiting LAG-3 expression. Our findings explain the sexual dimorphism in human autoimmunity, as CD2 associated with rheumatoid arthritis and its regulation through 17-β-estradiol was conserved in human T cells. Hormonal regulation of CD2 has implications for CD2-targeted therapy. Indeed, anti-CD2 treatment was more potent in female mice. In conclusion, our results demonstrate the relevance of sex-genotype interactions and provide strong evidence for CD2 as a sex-sensitive predisposing factor in autoimmunity.

scholarly journals Polymorphic estrogen receptor binding site causes Cd2-dependent sex bias in the susceptibility to autoimmune diseases

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Gonzalo Fernandez Lahore ◽  
Michael Förster ◽  
Martina Johannesson ◽  
Pierre Sabatier ◽  
Erik Lönnblom ◽  
...  
Keyword(s):  
T Cells ◽  
Estrogen Receptor ◽  
T Cell ◽  
Autoimmune Diseases ◽  
Binding Site ◽  
Receptor Binding ◽  
Receptor Binding Site ◽  
Female Mice ◽  
Estrogen Receptor Binding ◽  
Estrogen Receptor Binding Site

AbstractComplex autoimmune diseases are sexually dimorphic. An interplay between predisposing genetics and sex-related factors probably controls the sex discrepancy in the immune response, but the underlying mechanisms are unclear. Here we positionally identify a polymorphic estrogen receptor binding site that regulates Cd2 expression, leading to female-specific differences in T cell-dependent mouse models of autoimmunity. Female mice with reduced Cd2 expression have impaired autoreactive T cell responses. T cells lacking Cd2 costimulation upregulate inhibitory Lag-3. These findings help explain sexual dimorphism in human autoimmunity, as we find that CD2 polymorphisms are associated with rheumatoid arthritis and 17-β-estradiol-regulation of CD2 is conserved in human T cells. Hormonal regulation of CD2 might have implications for CD2-targeted therapy, as anti-Cd2 treatment more potently affects T cells in female mice. These results demonstrate the relevance of sex-genotype interactions, providing strong evidence for CD2 as a sex-sensitive predisposing factor in autoimmunity.

scholarly journals Potent sialic acid inhibitors that target influenza A virus hemagglutinin

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu-Jen Chang ◽  
Cheng-Yun Yeh ◽  
Ju-Chien Cheng ◽  
Yu-Qi Huang ◽  
Kai-Cheng Hsu ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Antiviral Activity ◽  
Binding Site ◽  
Influenza A Virus ◽  
Receptor Binding ◽  
Influenza A ◽  
The United States ◽  
Ligand Complex ◽  
Receptor Binding Site ◽  
Computational Strategy

AbstractEradicating influenza A virus (IAV) is difficult, due to its genetic drift and reassortment ability. As the infectious cycle is initiated by the influenza glycoprotein, hemagglutinin (HA), which mediates the binding of virions to terminal sialic acids moieties, HA is a tempting target of anti-influenza inhibitors. However, the complexity of the HA structure has prevented delineation of the structural characterization of the HA protein–ligand complex. Our computational strategy efficiently analyzed > 200,000 records of compounds held in the United States National Cancer Institute (NCI) database and identified potential HA inhibitors, by modeling the sialic acid (SA) receptor binding site (RBS) for the HA structure. Our modeling revealed that compound NSC85561 showed significant antiviral activity against the IAV H1N1 strain with EC50 values ranging from 2.31 to 2.53 µM and negligible cytotoxicity (CC50 > 700 µM). Using the NSC85561 compound as the template to generate 12 derivatives, robust bioassay results revealed the strongest antiviral efficacies with NSC47715 and NSC7223. Virtual screening clearly identified three SA receptor binding site inhibitors that were successfully validated in experimental data. Thus, our computational strategy has identified SA receptor binding site inhibitors against HA that show IAV-associated antiviral activity.

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