ArticleMolecular and cellular biology2005
Genetic deletion of the repressor of estrogen receptor activity (REA) enhances the response to estrogen in target tissues in vivo.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 96 citations in OpenAlex.
- Prohibitin 2 is a key regulator of T cell proliferation, differentiation, and effector functions in vivo.Communications biology · 2026Article
- Prohibitins: emerging host targets of bacteria and viruses at the plasma membrane, mitochondria, and cytoplasm.Microbial cell (Graz, Austria) · 2026Article
- Activation of AMP-activated protein kinase (AMPK) through inhibiting interaction with prohibitins.iScience · 2023Article
- Inhibition of Prolyl Oligopeptidase Restores Prohibitin 2 Levels in Psychosis Models: Relationship to Cognitive Deficits in Schizophrenia.International journal of molecular sciences · 2023Article
- Role of Prohibitins in Aging and Therapeutic Potential Against Age-Related Diseases.Frontiers in genetics · 2021Review
- Prohibitin S-Nitrosylation Is Required for the Neuroprotective Effect of Nitric Oxide in Neuronal Cultures.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Prohibitin 2 deficiency impairs cardiac fatty acid oxidation and causes heart failure.Cell death & disease · 2020Article
- Involvement of prohibitin 1 and prohibitin 2 upregulation in cBSA-induced podocyte cytotoxicity.Journal of food and drug analysis · 2020Article
- Article
- Prohibitin: a prime candidate for a pleiotropic effector that mediates sex differences in obesity, insulin resistance, and metabolic dysregulation.Biology of sex differences · 2019Review
- Neuronal expression of the mitochondrial protein prohibitin confers profound neuroprotection in a mouse model of focal cerebral ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Article
- The prohibitin protein complex promotes mitochondrial stabilization and cell survival in hematologic malignancies.Oncotarget · 2017Article
- Multiple Beneficial Roles of Repressor of Estrogen Receptor Activity (REA) in Suppressing the Progression of Endometriosis.Endocrinology · 2016Article
- Prohibitin: an unexpected role in sex dimorphic functions.Biology of sex differences · 2016Article
- A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation.Oncotarget · 2015Article
- Spatial mapping of juxtacrine axo-glial interactions identifies novel molecules in peripheral myelination.Nature communications · 2015Article
- Multifaceted role of prohibitin in cell survival and apoptosis.Apoptosis : an international journal on programmed cell death · 2015Review
- Recent insights into the actions of IGFBP-6.Journal of cell communication and signaling · 2015Article
- Estradiol inhibits Th17 cell differentiation through inhibition of RORγT transcription by recruiting the ERα/REA complex to estrogen response elements of the RORγT promoter.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Inhibition of insulin/IGF-1 receptor signaling protects from mitochondria-mediated kidney failure.EMBO molecular medicine · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
We previously identified a coregulator, repressor of estrogen receptor activity (REA), that directly interacts with estrogen receptor (ER) and represses ER transcriptional activity. Decreasing the intracellular level of REA by using small interfering RNA knockdown or antisense RNA approaches in cells in culture resulted in a significant increase in the level of up-regulation of estrogen-stimulated genes. To elucidate the functional activities of REA in vivo, we have used targeted disruption to delete the REA gene in mice. The targeting vector eliminated, by homologous recombination, the REA exon sequences encoding amino acids 12 to 201, which are required for REA repressive activity and for interaction with ER. The viability of heterozygous animals was similar to that of the wild type, whereas homozygous animals did not develop, suggesting a crucial role for REA in early development. Female, but not male, heterozygous animals had an increased body weight relative to age-matched wild-type animals beginning after puberty. REA mRNA and protein levels in uteri of heterozygous animals were half that of the wild type, and studies with heterozygous animals revealed a greater uterine weight gain and epithelial hyperproliferation in response to estradiol (E2) and a substantially greater stimulation by E2 of a number of estrogen up-regulated genes in the uterus. Even more dramatic in REA heterozygous animals was the loss of down regulation by E2 of genes in the uterus that are normally repressed by estrogen in wild-type animals. Mouse embryo fibroblasts derived from heterozygous embryos also displayed a greater transcriptional response to E2. These studies demonstrate that REA is a significant modulator of estrogen responsiveness in vivo: it normally restrains estrogen actions, moderating ER stimulation and enhancing ER repression of E2-regulated genes.
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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.