ArticleOncogene2013
Coordinate regulation of estrogen receptor β degradation by Mdm2 and CREB-binding protein in response to growth signals.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Nucleic sexual hormone receptor signaling pathways in breast cancer: function regulation, crosstalk, and therapeutic implications.NPJ precision oncology · 2026Review
- Role of androgen receptors in sexually dimorphic phenotypes in UBE3A-dependent autism spectrum disorder.iScience · 2025Article
- Computational identification of potential natural terpenoid inhibitors of MDM2 for breast cancer therapy: molecular docking, molecular dynamics simulation, and ADMET analysis.Frontiers in chemistry · 2025Article
- SUMOylation of nuclear receptor Nor1/NR4A3 coordinates microtubule cytoskeletal dynamics and stability in neuronal cells.Cell & bioscience · 2024Article
- Sexually dimorphic phenotypes and the role of androgen receptors in UBE3A-dependent autism spectrum disorder.bioRxiv : the preprint server for biology · 2024Article
- WFDC3 inhibits tumor metastasis by promoting the ERβ-mediated transcriptional repression of TGFBR1 in colorectal cancer.Cell death & disease · 2023Article
- Fetal Cardiac Lipid Sensing Triggers an Early and Sex-related Metabolic Energy Switch in Intrauterine Growth Restriction.The Journal of clinical endocrinology and metabolism · 2021Article
- Estrogen Receptors and Ubiquitin Proteasome System: Mutual Regulation.Biomolecules · 2020Review
- Estrogen Receptor Beta (ERβ): A Ligand Activated Tumor Suppressor.Frontiers in oncology · 2020Review
- The role of estrogen receptor beta in breast cancer.Biomarker research · 2020Review
- Pyk2 deficiency potentiates osteoblast differentiation and mineralizing activity in response to estrogen or raloxifene.Molecular and cellular endocrinology · 2018Article
- Feedback control of the CXCR7/CXCL11 chemokine axis by estrogen receptor α in ovarian cancer.Molecular oncology · 2018Article
- A CK2-RNF4 interplay coordinates non-canonical SUMOylation and degradation of nuclear receptor FXR.Journal of molecular cell biology · 2017Article
- The role of MDM2 and MDM4 in breast cancer development and prevention.Journal of molecular cell biology · 2017Review
- Proximal and distal regulation of the HYAL1 gene cluster by the estrogen receptor α in breast cancer cells.Oncotarget · 2016Article
- Estrogen receptor alpha (ERα/ESR1) mediates the p53-independent overexpression of MDM4/MDMX and MDM2 in human breast cancer.Oncotarget · 2016Article
- Reciprocal Regulation of ERα and ERβ Stability and Activity by Diptoindonesin G.Chemistry & biology · 2015Article
- MTA1 regulation of ERβ pathway in salivary gland carcinoma cells.Biochemical and biophysical research communications · 2015Article
- Ubiquitylation of nuclear receptors: new linkages and therapeutic implications.Journal of molecular endocrinology · 2015Review
- Subcellular localization of Mdm2 expression and prognosis of breast cancer.International journal of clinical oncology · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The biological actions of estrogen are mediated via estrogen receptors ERα and ERβ. Yet, other cellular signaling events that also impact ER functions have an important role in breast carcinogenesis. Here, we show that activation of ErbB2/ErbB3 tyrosine kinase receptors with growth factor heregulin-β prompts ERβ degradation by the 26S proteasome, a mechanism that requires the coactivator cAMP response element-binding (CREB)-binding protein (CBP). We found that CBP promotes ERβ ubiquitination and degradation through enhancement of the PI3-K/Akt pathway by heregulin-β, an effect potentiated by a negatively charged hinge region of ERβ. Activated Akt triggered the recruitment of E3 ubiquitin ligase Mdm2 to ERβ, which was further stabilized by CBP, resulting in ERβ poly-ubiquitination. Mutation of CBP Thr-1872 or Mdm2 Ser-186/188 Akt sites resulted in a dissociation of the ERβ-CBP-Mdm2 complex and reduced ERβ turnover. We found that the decrease in ERβ induced by heregulin-β was associated with reduced target gene promoter occupancy and enhanced proliferation of breast cancer cells. However, knockdown of Mdm2 restored endogenous ERβ levels resulting in reduction of breast cancer cell growth. These studies identify a tripartite Akt-regulated phosphorylation mechanism that functions to hamper normal ERβ activity and turnover through the concerted actions of CBP and Mdm2 in response to growth factor signaling pathways in breast cancer cells.
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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.