ArticleThe Journal of biological chemistry2010
Down-regulation of PROS1 gene expression by 17beta-estradiol via estrogen receptor alpha (ERalpha)-Sp1 interaction recruiting receptor-interacting protein 140 and the corepressor-HDAC3 complex.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
39 citing papers in PubMed, 87 citations in OpenAlex.
- Impact of Estetrol Combined with Drospirenone on Blood Coagulation and Fibrinolysis in Patients with Endometriosis: A Multicenter, Randomized, Open-Label, Active-Controlled, Parallel-Group Study.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisTrial
- Protein S: a vitamin K-dependent factor bridging haemostasis, tissue homeostasis and cancer.The Biochemical journal · 2026Review
- Estrogen and obesity synergistically suppress protein S via HIF1α, enhancing thrombosis potential.The Journal of clinical investigation · 2025Article
- Involvement of nuclear receptor corepressor 2 (NCOR2) in estrogen-induced repression of arcuate Kiss1 expression in female rats.The Journal of reproduction and development · 2025Article
- Activation of Genes by Nuclear Receptor/Specificity Protein (Sp) Interactions in Cancer.Cancers · 2025Review
- Functions of TAM Receptors and Ligands Protein S and Gas6 in Atherosclerosis and Cardiovascular Disease.International journal of molecular sciences · 2024Review
- Hdac3 deficiency limits periosteal reaction associated with Western diet feeding in female mice.Journal of cellular and molecular medicine · 2024Article
- HDAC-driven mechanisms in anticancer resistance: epigenetics and beyond.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- The Role of TAM Receptors in Bone.International journal of molecular sciences · 2023Review
- Polyamine Oxidase Expression Is Downregulated by 17β-Estradiol via Estrogen Receptor 2 in Human MCF-7 Breast Cancer Cells.International journal of molecular sciences · 2022Article
- YciR, a Specific 3'-Phosphodiesterase, Plays a Role in the Pathogenesis of UropathogenicFrontiers in microbiology · 2022Article
- Venous thromboembolism associated with combined oral contraceptive use: a single-institution experience.Obstetrics & gynecology science · 2021Article
- Comparative evaluation of reagents for measuring protein S activity: possibility of harmonization.International journal of hematology · 2021Article
- Acute Nonatherosclerotic Coronary Thromboembolism Presenting with an Inferior STEMI in a Patient on Oral Contraception.Case reports in cardiology · 2021Article
- Estrogen Reverses HDAC Inhibitor-Mediated Repression ofFrontiers in immunology · 2020Article
- Amlodipine induces vasodilation via Akt2/Sp1-activated miR-21 in smooth muscle cells.British journal of pharmacology · 2019Article
- Effects of low-dose combined oral contraceptives and protein S K196E mutation on anticoagulation factors: a prospective observational study.International journal of hematology · 2019Observational
- Review
- Hypoxia downregulates protein S expression.Blood · 2018Article
- Correlates of plasma and platelet tissue factor pathway inhibitor, factor V, and Protein S.Research and practice in thrombosis and haemostasis · 2018Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pregnant women show a low level of protein S (PS) in plasma, which is known to be a risk for deep venous thrombosis. 17Beta-estradiol (E(2)), an estrogen that increases in concentration in the late stages of pregnancy, regulates the expression of various genes via the estrogen receptor (ER). Here, we investigated the molecular mechanisms behind the reduction in PS levels caused by E(2) in HepG2-ERalpha cells, which stably express ERalpha, and also the genomic ER signaling pathway, which modulates the ligand-dependent repression of the PSalpha gene (PROS1). We observed that E(2) repressed the production of mRNA and antigen of PS. A luciferase reporter assay revealed that E(2) down-regulated PROS1 promoter activity and that this E(2)-dependent repression disappeared upon the deletion or mutation of two adjacent GC-rich motifs in the promoter. An electrophoretic mobility shift assay and DNA pulldown assay revealed that the GC-rich motifs were associated with Sp1, Sp3, and ERalpha. In a chromatin immunoprecipitation assay, we found ERalpha-Sp protein-promoter interaction involved in the E(2)-dependent repression of PROS1 transcription. Furthermore, we demonstrated that E(2) treatment recruited RIP140 and the NCoR-SMRT-HDAC3 complex to the PROS1 promoter, which hypoacetylated chromatin. Taken together, this suggested that E(2) might repress PROS1 transcription depending upon ERalpha-Sp1 recruiting transcriptional repressors in HepG2-ERalpha cells and, consequently, that high levels of E(2) leading to reduced levels of plasma PS would be a risk for deep venous thrombosis in pregnant women.
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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.