ArticleProceedings of the National Academy of Sciences of the United States of America2011
Activation function 2 (AF2) of estrogen receptor-alpha is required for the atheroprotective action of estradiol but not to accelerate endothelial healing.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 114 citations in OpenAlex.
- A Universal Plasticizer Alkylsulfonic Phenyl Ester Activates Pregnane X Receptor to Increase Intestinal Cholesterol Uptake.International journal of molecular sciences · 2026Article
- Endothelial Estrogen Receptor Alpha Inhibits Plaque Inflammation in Both Sexes.Circulation research · 2026Article
- Microplastic exposure elicits sex-specific atherosclerosis development in lean low-density lipoprotein receptor-deficient mice.Environment international · 2025Article
- Endothelial oestrogen-myocardial cyclic guanosine monophosphate axis critically determines angiogenesis and cardiac performance during pressure overload.Cardiovascular research · 2024Article
- Unraveling the Dynamics of Estrogen and Progesterone Signaling in the Endometrium: An Overview.Cells · 2024Review
- Reprogramming of endothelial gene expression by tamoxifen inhibits angiogenesis and ERα-negative tumor growth.Theranostics · 2024Article
- Membrane estrogen receptor α signaling modulates the sensitivity to estradiol treatment in a dose- and tissue- dependent manner.Scientific reports · 2023Article
- Tie2-Cre-Induced Inactivation of Non-Nuclear Estrogen Receptor-α Signaling Abrogates Estrogen Protection Against Vascular Injury.JACC. Basic to translational science · 2023Article
- The emerging role of estrogen's non-nuclear signaling in the cardiovascular disease.Frontiers in cardiovascular medicine · 2023Review
- Loss of function of the maternal membrane oestrogen receptor ERα alters expansion of trophoblast cells and impacts mouse fertility.Development (Cambridge, England) · 2022Article
- Estrogen Receptor Function: Impact on the Human Endometrium.Frontiers in endocrinology · 2022Review
- The physiological role of estrogen receptor functional domains.Essays in biochemistry · 2021Review
- Article
- Nuclear Receptors and Clock Components in Cardiovascular Diseases.International journal of molecular sciences · 2021Review
- Estetrol and Mammary Gland: Friends or Foes?Journal of mammary gland biology and neoplasia · 2021Review
- Estrogen receptor-α signaling in post-natal mammary development and breast cancers.Cellular and molecular life sciences : CMLS · 2021Review
- Critical Role of Estrogens on Bone Homeostasis in Both Male and Female: From Physiology to Medical Implications.International journal of molecular sciences · 2021Review
- Sex Differences and Regulatory Actions of Estrogen in Cardiovascular System.Frontiers in physiology · 2021Review
- Estrogen Receptor and Vascular Aging.Frontiers in aging · 2021Review
- Proteolysis-targeting chimeras and their implications in breast cancer.Exploration of targeted anti-tumor therapy · 2021Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
17β-Estradiol (E2) regulates estrogen receptor-α (ERα) target gene transcription through the two independent activation functions (AFs), AF1 and AF2, located in the N-terminal and ligand binding domain of ERα, respectively. We previously reported that ERα is required for the E2 atheroprotective action as well as for its accelerative action on endothelial healing, but its AF1 function is dispensable. Here, we investigated the role of ERαAF2 in these two major beneficial actions of E2 by electively targeting ERαAF2 (named ERαAF2(0)). Our results prove four points. (i) Compared with WT ERα, the ability of ERαAF2(0) to stimulate the C3 complement or the estrogen response element-thymidine kinase promoter in two cell lines was dramatically decreased, confirming the importance of AF2 in the E2-induced transcriptional activity of ERα. (ii) The uterotrophic action of E2 was totally absent in ERαAF2(0) mice, showing the crucial role of ERαAF2 in E2-induced uterus hyperplasia. (iii) ERαAF2 was dispensable for the accelerative action of E2 on endothelial healing, underlining the functionality of ERαAF2(0) in vivo. (iv) Finally, the atheroprotective effect of E2 was abrogated in ERαAF2(0) LDL-r(-/-) mice. Thus, whereas ERαAF1 and ERαAF2 are both required for the uterotrophic action of E2, we show that only ERαAF2 is necessary for its atheroprotective effect.
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