ArticleProceedings of the National Academy of Sciences of the United States of America1999
Proteasome-dependent degradation of the human estrogen receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers.
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Who cites it
201 citing papers in PubMed, 584 citations in OpenAlex.
- Gender Bias in Human Systemic Lupus Erythematosus: A Problem of Steroid Receptor Action?Frontiers in immunology · 2018Trial
- Phytoestrogens/insoluble fibers and colonic estrogen receptor β: randomized, double-blind, placebo-controlled study.World journal of gastroenterology · 2013Trial
- A phase II study of 17-allylamino-17-demethoxygeldanamycin in metastatic or locally advanced, unresectable breast cancer.Breast cancer research and treatment · 2012Trial
- Mechanisms for Mineralocorticoid-Driven Age-Related Hypertension: Potential Therapeutic Role of Mineralocorticoid Receptor Antagonists and Aldosterone Synthase Inhibitors.Circulation research · 2026Review
- CDKN1B inactivation impacts ER signaling and drives resistance to endocrine therapy in breast cancer.British journal of cancer · 2026Article
- Layered Single-Cell Heterogeneity in Hormone Receptor Signaling Across Mouse Organoids and Human ERα+ Cancer Cells.bioRxiv : the preprint server for biology · 2026Article
- Allosteric Induction of Estrogen Receptor Ligand Binding Domain Tetramerization by a Distinct Complete Estrogen Receptor Antagonist.ACS medicinal chemistry letters · 2026Article
- Mutant p53 binds and controls estrogen receptor activity to drive endocrine resistance in ovarian cancer.Genes & development · 2026Article
- Silencing lipid catabolism determines longevity in response to fasting.Nature communications · 2026Article
- Discovery of a novel small molecule degrader of wild type and mutant estrogen receptors using DNA encoded libraries.NPJ breast cancer · 2025Article
- Preclinical Efficacy of the Estrogen Receptor Degrader Fulvestrant in Combination with RAF/MEK Clamp Avutometinib and FAK Inhibitor in a Low-Grade Serous Ovarian Cancer Animal Model with Acquired Resistance to Chemotherapy and Aromatase Inhibitor.International journal of molecular sciences · 2025Article
- Comprehensive functional annotation of ESR1-driven enhancers in breast cancer reveals hierarchical activity independent of genomic and epigenomic contexts.Genome research · 2025Article
- Article
- Context-Dependent Estrogenic Actions of (+)-Pisatin Produced in Elicited Green or Snow Pea (Journal of agricultural and food chemistry · 2024Article
- Targeted protein degradation: from mechanisms to clinic.Nature reviews. Molecular cell biology · 2024Review
- Effects of Curcumin and Estrogen Receptor Alpha in Luminal Breast Cancer Cells.Diagnostics (Basel, Switzerland) · 2024Article
- Article
- The role of glia in the dysregulation of neuronal spinogenesis in Ube3a-dependent ASD.Experimental neurology · 2024Article
- Proteasome Inhibition Reprograms Chromatin Landscape in Breast Cancer.Cancer research communications · 2024Article
- TRIM33 Is a Co-Regulator of Estrogen Receptor Alpha.Cancers · 2024Article
141 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In eukaryotic cells, the ubiquitin-proteasome pathway is the major mechanism for the targeted degradation of proteins with short half-lives. The covalent attachment of ubiquitin to lysine residues of targeted proteins is a signal for the recognition and rapid degradation by the proteasome, a large multi-subunit protease. In this report, we demonstrate that the human estrogen receptor (ER) protein is rapidly degraded in mammalian cells in an estradiol-dependent manner. The treatment of mammalian cells with the proteasome inhibitor MG132 inhibits activity of the proteasome and blocks ER degradation, suggesting that ER protein is turned over through the ubiquitin-proteasome pathway. In addition, we show that in vitro ER degradation depends on ubiquitin-activating E1 enzyme (UBA) and ubiquitin-conjugating E2 enzymes (UBCs), and the proteasome inhibitors MG132 and lactacystin block ER protein degradation in vitro. Furthermore, the UBA/UBCs and proteasome inhibitors promote the accumulation of higher molecular weight forms of ER. The UBA and UBCs, which promote ER degradation in vitro, have no significant effect on human progesterone receptor and human thyroid hormone receptor beta proteins.
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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.