ArticleProceedings of the National Academy of Sciences of the United States of America2005
Estrogen down-regulation of the corepressor N-CoR: mechanism and implications for estrogen derepression of N-CoR-regulated genes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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
43 citing papers in PubMed, 81 citations in OpenAlex.
- Host cell factors stimulate HIV-1 transcription by antagonizing substrate-binding function of Siah1 ubiquitin ligase to stabilize transcription elongation factor ELL2.Nucleic acids research · 2020Article
- DeSUMOylase SENP7-Mediated Epithelial Signaling Triggers Intestinal Inflammation via Expansion of Gamma-Delta T Cells.Cell reports · 2019Article
- Structurally Diverse Histone Deacetylase Photoreactive Probes: Design, Synthesis, and Photolabeling Studies in Live Cells and Tissue.ChemMedChem · 2019Article
- Siah2 modulates sex-dependent metabolic and inflammatory responses in adipose tissue to a high-fat diet challenge.Biology of sex differences · 2019Article
- Genomic-Epidemiologic Evidence That Estrogens Promote Breast Cancer Development.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2018Article
- A quantitative mass spectrometry-based approach to monitor the dynamics of endogenous chromatin-associated protein complexes.Nature communications · 2018Article
- The SIAH E3 ubiquitin ligases promote Wnt/β-catenin signaling through mediating Wnt-induced Axin degradation.Genes & development · 2017Article
- Seven in Absentia E3 Ubiquitin Ligases: Central Regulators of Neural Cell Fate and Neuronal Polarity.Frontiers in cellular neuroscience · 2017Review
- Agonists and knockdown of estrogen receptor β differentially affect invasion of triple-negative breast cancer cells in vitro.BMC cancer · 2016Article
- Article
- ETS2 and Twist1 promote invasiveness of Helicobacter pylori-infected gastric cancer cells by inducing Siah2.The Biochemical journal · 2016Article
- Moving Toward Integrating Gene Expression Profiling Into High-Throughput Testing: A Gene Expression Biomarker Accurately Predicts Estrogen Receptor α Modulation in a Microarray Compendium.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- SIAH2 protein expression in breast cancer is inversely related with ER status and outcome to tamoxifen therapy.American journal of cancer research · 2016Article
- Nuclear receptors and the Warburg effect in cancer.International journal of cancer · 2015Review
- SIAH ubiquitin ligases regulate breast cancer cell migration and invasion independent of the oxygen status.Cell cycle (Georgetown, Tex.) · 2015Article
- Nuclear receptor corepressor complexes in cancer: mechanism, function and regulation.American journal of clinical and experimental urology · 2014Review
- Investigating the molecular basis of Siah1 and Siah2 E3 ubiquitin ligase substrate specificity.PloS one · 2014Article
- SIAH ubiquitin ligases target the nonreceptor tyrosine kinase ACK1 for ubiquitinylation and proteasomal degradation.Oncogene · 2013Article
- Regulators and effectors of Siah ubiquitin ligases.Cell biochemistry and biophysics · 2013Review
- Structure-based design of covalent Siah inhibitors.Chemistry & biology · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The nuclear receptor corepressor N-CoR plays a crucial role in the repressive activity of diverse transcription factors, yet little is known about what regulates its cellular level. We have found that estrogen markedly down-regulates N-CoR protein levels in estrogen receptor (ER)-positive breast cancer cells without affecting N-CoR mRNA levels, whereas levels of the related corepressor SMRT are unaffected. This effect is attributable to estrogen up-regulation of the ubiquitin ligase Siah2, which is a rapid and primary transcriptional response mediated by the ER, and precedes the loss of N-CoR. Treatment with proteasomal inhibitor or with small interfering RNA against Siah2 prevented the down-regulation of N-CoR by estrogen. Furthermore, the expression of 24-hydroxylase, a gene repressed by unliganded vitamin D receptor through its interaction with N-CoR, was up-regulated by estrogen and required Siah2. Our results illustrate a mechanism by which the estrogen-ER complex markedly reduces the level of N-CoR through a process involving the up-regulation of Siah2 and the subsequent targeting of N-CoR for proteasomal degradation. These findings reveal that, although estrogen directly regulates the transcription of many genes, by regulating a gene such as Siah2 it can exert profound "secondary" effects on cellular activity through mechanisms such as targeting regulatory proteins for degradation. This estrogen-evoked down-regulation of N-CoR could have a global derepressive effect on genes whose repression depends on N-CoR and thereby have broad impact on the activity of transcription factors and nuclear receptors whose actions involve N-CoR.
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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.