ArticleThe Journal of biological chemistry2015
Transactivation Function-2 of Estrogen Receptor α Contains Transactivation Function-1-regulating Element.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- Bazedoxifene and Beyond: Identifying This SERM's Targets and Deciphering Its Molecular Mechanisms.Advances in pharmacological and pharmaceutical sciences · 2026Review
- Exploring the Complex Mechanisms of Isoflavones: From Cell Bioavailability, to Cell Dynamics and Breast Cancer.Phytotherapy research : PTR · 2025Review
- The physiological role of estrogen receptor functional domains.Essays in biochemistry · 2021Review
- Estrogen and estrogen receptors in kidney diseases.Renal failure · 2021Review
- The genomic regulatory elements for estrogen receptor alpha transactivation-function-1 regulated genes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Long-Term Follow-Up and Treatment of a Female With Complete Estrogen Insensitivity.The Journal of clinical endocrinology and metabolism · 2020Article
- Transactivation Function-1-Mediated Partial Agonist Activity of Selective Estrogen Receptor Modulator Requires Homo-Dimerization of the Estrogen Receptor α Ligand Binding Domain.International journal of molecular sciences · 2019Review
- Article
- Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay.Journal of visualized experiments : JoVE · 2018Article
- Estrogen Receptors: New Directions in the New Millennium.Endocrine reviews · 2018Review
- Estrogen in the male: a historical perspective.Biology of reproduction · 2018Review
- The F domain of estrogen receptor α is involved in species-specific, tamoxifen-mediated transactivation.The Journal of biological chemistry · 2018Article
- Hormone signaling and fatty liver in females: analysis of estrogen receptor α mutant mice.International journal of obesity (2005) · 2017Article
- Antiestrogens: structure-activity relationships and use in breast cancer treatment.Journal of molecular endocrinology · 2017Review
- Estrogen Hormone Biology.Current topics in developmental biology · 2017Review
- Tyrosine phosphorylation regulates ERβ ubiquitination, protein turnover, and inhibition of breast cancer.Oncotarget · 2016Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
ERα has a ligand-dependent transactivation function in the ligand binding domain of ERα C terminus (AF-2) and a ligand-independent activation function in the N terminus (AF-1). It is still not fully understood how AF-1 and AF-2 activities are regulated cooperatively by ligands. To evaluate the AF-1 involvement in the estrogenic activities of various compounds, we analyzed these transactivation functions using AF-1-truncated and AF-2-mutated ERα mutants. AF-2 is composed of two domains with flexible and static regions. We used an AF-2 flexible region mutant and an AF-2 static region mutant. Both mutants have been reported as non-E2 responsive due to disruption of E2-mediated coactivator recruitment to the AF-2. The AF-2 mutants were not activated by agonists, but surprisingly antagonists and selective estrogen receptor modulators (SERMs) activated the AF-2 mutants. This antagonist reversal activity was derived from AF-1. Furthermore, we demonstrated that the AF-2 contains an AF-1 suppression function using C-terminal-truncated ERα mutants. From these findings we hypothesized that the mutation of AF-2 disrupted its ability to suppress AF-1, causing the antagonist reversal. To assess the AF-2-mediated AF-1 suppression, we analyzed the transcription activity of physically separated AF-1 and AF-2 using a novel hybrid reporter assay. We observed that the AF-1 activity was not suppressed by the physically separated AF-2. Furthermore, SERMs did not induce the AF-1-mediated activity from the separated mutant AF-2, which differed from the intact protein. These results imply that SERM activity is dependent on a conformational change of the full-length ERα molecule, which allows for AF-1 activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.