ArticleThe Journal of clinical investigation2018
Fbxo22-mediated KDM4B degradation determines selective estrogen receptor modulator activity in breast cancer.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 75 citations in OpenAlex.
- The JMJD family histone demethylases: structure, mechanism of action, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- Histone lysine demethylases in breast cancer: molecular mechanisms, biological functions, and therapeutic intervention.Molecular cancer · 2025Review
- FBXO22 deficiency defines a pleiotropic syndrome of growth restriction and multi-system anomalies associated with a unique epigenetic signature.American journal of human genetics · 2025Article
- F-box in breast cancer: mechanism of action and therapeutic potential.American journal of translational research · 2025Review
- A CRISPR activation screen identifies FBXO22 supporting targeted protein degradation.Nature chemical biology · 2024Article
- Ribosomal S6 kinase (RSK) plays a critical role in DNA damage response via the phosphorylation of histone lysine demethylase KDM4B.Breast cancer research : BCR · 2024Article
- FBXO22 promotes osteosarcoma progression via regulation of FOXO1 for ubiquitination and degradation.Journal of cellular and molecular medicine · 2024Article
- To Erase or Not to Erase: Non-Canonical Catalytic Functions and Non-Catalytic Functions of Members of Histone Lysine Demethylase Families.International journal of molecular sciences · 2024Review
- FBXO22 is a potential therapeutic target for recurrent chondrosarcoma.Journal of bone oncology · 2024Article
- Potential role of Fbxo22 in resistance to endocrine therapy in breast cancer with invasive lobular carcinoma.Breast cancer research and treatment · 2024Article
- Targeting FBXO22 enhances radiosensitivity in non-small cell lung cancer by inhibiting the FOXM1/Rad51 axis.Cell death & disease · 2024Article
- LONRF2 is a protein quality control ubiquitin ligase whose deficiency causes late-onset neurological deficits.Nature aging · 2023Article
- Fbxo22 inhibits metastasis in triple-negative breast cancer through ubiquitin modification of KDM5A and regulation of H3K4me3 demethylation.Cell biology and toxicology · 2023Article
- The crosstalk between ubiquitination and endocrine therapy.Journal of molecular medicine (Berlin, Germany) · 2023Review
- FBXO22 promotes leukemogenesis by targeting BACH1 in MLL-rearranged acute myeloid leukemia.Journal of hematology & oncology · 2023Article
- KDM4 Demethylases: Structure, Function, and Inhibitors.Advances in experimental medicine and biology · 2023Article
- Pharmacokinetic Study of Conjugated Equine Estrogens in Healthy Chinese Postmenopausal Women Using a Parallel Two-Column LC-MS/MS Method.Clinical pharmacokinetics · 2022Article
- Host F-Box Protein 22 Enhances the Uptake of Brucella by Macrophages and Drives a Sustained Release of Proinflammatory Cytokines through Degradation of the Anti-Inflammatory Effector Proteins of Brucella.Infection and immunity · 2022Article
- Global identification of phospho-dependent SCF substrates reveals a FBXO22 phosphodegron and an ERK-FBXO22-BAG3 axis in tumorigenesis.Cell death and differentiation · 2022Article
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The agonistic/antagonistic biocharacter of selective estrogen receptor modulators (SERMs) can have therapeutic advantages, particularly in the case of premenopausal breast cancers. Although the contradictory effects of these modulators have been studied in terms of crosstalk between the estrogen receptor α (ER) and coactivator dynamics and growth factor signaling, the molecular basis of these mechanisms is still obscure. We identify a series of regulatory mechanisms controlling cofactor dynamics on ER and SERM function, whose activities require F-box protein 22 (Fbxo22). Skp1, Cullin1, F-box-containing complex (SCFFbxo22) ubiquitylated lysine demethylase 4B (KDM4B) complexed with tamoxifen-bound (TAM-bound) ER, whose degradation released steroid receptor coactivator (SRC) from ER. Depletion of Fbxo22 resulted in ER-dependent transcriptional activation via transactivation function 1 (AF1) function, even in the presence of SERMs. In living cells, TAM released SRC and KDM4B from ER in a Fbxo22-dependent manner. SRC release by TAM required Fbxo22 on almost all ER-SRC-bound enhancers and promoters. TAM failed to prevent the growth of Fbxo22-depleted, ER-positive breast cancers both in vitro and in vivo. Clinically, a low level of Fbxo22 in tumor tissues predicted a poorer outcome in ER-positive/human epidermal growth factor receptor type 2-negative (HER2-negative) breast cancers with high hazard ratios, independently of other markers such as Ki-67 and node status. We propose that the level of Fbxo22 in tumor tissues defines a new subclass of ER-positive breast cancers for which SCFFbxo22-mediated KDM4B degradation in patients can be a therapeutic target for the next generation of SERMs.
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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.