ArticleThe EMBO journal1997
Ligand-independent activation of the oestrogen receptor by mutation of a conserved tyrosine.
Article in The EMBO journal, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 124 citations in OpenAlex.
- Ligand-Dependent and -Independent Functions of Activation Function 1 of Progesterone Receptor in Genome-Wide Gene Regulation and in Cell Proliferation and Apoptosis of Breast Cancer Cells.International journal of molecular sciences · 2026Article
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- The physiological role of estrogen receptor functional domains.Essays in biochemistry · 2021Review
- Structural underpinnings of oestrogen receptor mutations in endocrine therapy resistance.Nature reviews. Cancer · 2018Review
- Genomic modelling of the ESR1 Y537S mutation for evaluating function and new therapeutic approaches for metastatic breast cancer.Oncogene · 2017Article
- Survey of phosphorylation near drug binding sites in the Protein Data Bank (PDB) and their effects.Proteins · 2015Article
- Estrogen receptor α in cancer-associated fibroblasts suppresses prostate cancer invasion via modulation of thrombospondin 2 and matrix metalloproteinase 3.Carcinogenesis · 2014Article
- Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor-positive breast cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- Vestigialization of an allosteric switch: genetic and structural mechanisms for the evolution of constitutive activity in a steroid hormone receptor.PLoS genetics · 2014Article
- Article
- Article
- Review
- Development of a novel molecular sensor for imaging estrogen receptor-coactivator protein-protein interactions.PloS one · 2012Article
- Classical estrogen receptor alpha signaling mediates negative and positive feedback on gonadotropin-releasing hormone neuron firing.Endocrinology · 2008Article
- c-Src-null mice exhibit defects in normal mammary gland development and ERalpha signaling.Oncogene · 2005Article
- Loss of ERbeta expression as a common step in estrogen-dependent tumor progression.Endocrine-related cancer · 2004Review
- Probing protein conformational changes in living cells by using designer binding proteins: application to the estrogen receptor.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- Estrogen receptor interaction with estrogen response elements.Nucleic acids research · 2001Review
- Heat shock protein 90 and the nuclear transport of progesterone receptor.Cell stress & chaperones · 2001Article
- CIA, a novel estrogen receptor coactivator with a bifunctional nuclear receptor interacting determinant.Molecular and cellular biology · 2001Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The oestrogen receptor is a member of the nuclear receptor family of transcription factors which, on binding the steroid hormone 17beta-oestradiol, interacts with co-activator proteins and stimulates gene expression. Replacement of a single tyrosine in the hormone-binding domain generated activated forms of the receptor which stimulated transcription in the absence of hormone. This increased activation is related to a decrease in hydrophobicity and a reduction in size of the side chain of the amino acid with which the tyrosine is replaced. Ligand-independent, in common with ligand-dependent transcriptional activation, requires an amphipathic alpha-helix at the C-terminus of the ligand-binding domain which is essential for the interaction of the receptor with a number of potential co-activator proteins. In contrast to the wild-type protein, constitutively active receptors were able to bind both the receptor-interacting protein RIP-140 and the steroid receptor co-activator SRC-1 in a ligand-independent manner, although in the case of SRC-1 this was only evident when the receptors were prebound to DNA. We propose, therefore, that this tyrosine is required to maintain the receptor in a transcriptionally inactive state in the absence of hormone. Modification of this residue may generate a conformational change in the ligand-binding domain of the receptor to form an interacting surface which allows the recruitment of co-activators independent of hormone binding. This suggests that this tyrosine may be a target for a different signalling pathway which forms an alternative mechanism of activating oestrogen receptor-mediated transcription.
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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.