ArticleMolecular endocrinology (Baltimore, Md.)2010
BRCA1 regulates acetylation and ubiquitination of estrogen receptor-alpha.
Article in Molecular endocrinology (Baltimore, Md.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 138 citations in OpenAlex.
- The Landscape of BRCA1-Associated Post-Translational Modifications.Cell biology international · 2026Review
- Nucleic sexual hormone receptor signaling pathways in breast cancer: function regulation, crosstalk, and therapeutic implications.NPJ precision oncology · 2026Review
- Human Cancers Derived from Either Genetic or Lifestyle Factors Are Initiated by Impaired Estrogen Signaling.Cancers · 2025Review
- A New Class of BRCA1 Mimetics for ERα-Positive Breast Cancer Therapy: Design, Synthesis, In Silico Screening, In Vitro Assay, and Gene Expression Analysis.Life (Basel, Switzerland) · 2025Article
- Decoding estrogen receptor and GPER biology: structural insights and therapeutic advances in ERα-positive breast cancer.Frontiers in oncology · 2025Review
- Effects of Endocrine Interventions Targeting ERα or PR on Breast Cancer Risk in the General Population and Carriers ofInternational journal of molecular sciences · 2024Review
- Review
- Progress and prospects in research and clinical practice of hormone receptor-positive, HER-2-negative breast cancer with BRCA1/2 mutations.Discover oncology · 2023Review
- Review
- The E3 Ligase TRIM4 Facilitates SET Ubiquitin-Mediated Degradation to Enhance ER-α Action in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Article
- FKBP52 and FKBP51 differentially regulate the stability of estrogen receptor in breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Decoding the Therapeutic Implications of the ERα Stability and Subcellular Distribution in Breast Cancer.Frontiers in endocrinology · 2022Review
- Modulation of BRCA1 mediated DNA damage repair by deregulated ER-α signaling in breast cancers.American journal of cancer research · 2022Article
- BRCA1-BARD1 regulates transcription through modulating topoisomerase IIβ.Open biology · 2021Article
- The BRCA1/BARD1 ubiquitin ligase and its substrates.The Biochemical journal · 2021Review
- USP35, regulated by estrogen and AKT, promotes breast tumorigenesis by stabilizing and enhancing transcriptional activity of estrogen receptor α.Cell death & disease · 2021Article
- Systematic characterization of mutations altering protein degradation in human cancers.Molecular cell · 2021Article
- Letrozole and zoledronic acid changed signalling pathways involved in the apoptosis of breast cancer cells.Journal of Taibah University Medical Sciences · 2021Article
- Non-Genomic Actions of Estrogens on the DNA Repair Pathways Are Associated With Chemotherapy Resistance in Breast Cancer.Frontiers in oncology · 2021Review
30 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Inherited mutations of the breast cancer susceptibility gene BRCA1 confer a high risk for breast cancer development. The (300)RXKK and (266)KXK motifs have been identified previously as sites for acetylation of the estrogen receptor-alpha (ER-alpha), and (302)K was also found to be a site for BRCA1-mediated mono-ubiquitination of ER-alpha in vitro. Here we show that ER-alpha proteins with single or double lysine mutations of these motifs (including K303R, a cancer-associated mutant) are resistant to inhibition by BRCA1, even though the mutant ER-alpha proteins retain the ability to bind to BRCA1. We also found that BRCA1 overexpression reduced and knockdown increased the level of acetylated wild-type ER-alpha, without changing the total ER-alpha protein level. Increased acetylation of ER-alpha due to BRCA1 small interfering RNA was dependent upon phosphatidylinositol 3-kinase/Akt signaling and on up-regulation of the coactivator p300. In addition, using an in vitro acetylation assay, we found that in vitro-translated wild-type BRCA1 but not a cancer-associated point mutant (C61G) inhibited p300-mediated acetylation of ER-alpha. Furthermore, BRCA1 overexpression increased the levels of mono-ubiquitinated ER-alpha protein, and a BRCA1 mutant that is defective for ubiquitin ligase activity but retains other BRCA1 functions (I26A) did not ubiquitinate ER-alpha or repress its activity in vivo. Finally, ER-alpha proteins with mutations of the (300)RXKK or (266)KXK motifs showed modest or no BRCA1-induced ubiquitination. We propose a model in which BRCA1 represses ER-alpha activity, in part, by regulating the relative degree of acetylation vs. ubiquitination of ER-alpha.
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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.