ArticleNature communications2017
Modulation of nongenomic activation of PI3K signalling by tetramerization of N-terminally-cleaved RXRα.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- RXRActa pharmaceutica Sinica. B · 2025Article
- Article
- Sulindac (K-80003) with nab-paclitaxel and gemcitabine overcomes drug-resistant pancreatic cancer.Molecular cancer · 2024Article
- Retinoid X receptor heterodimers in hepatic function: structural insights and therapeutic potential.Frontiers in pharmacology · 2024Review
- The Use of Retinoids for the Prevention and Treatment of Skin Cancers: An Updated Review.International journal of molecular sciences · 2022Review
- Recent applications of computational methods to allosteric drug discovery.Frontiers in molecular biosciences · 2022Review
- Phase separation of Nur77 mediates celastrol-induced mitophagy by promoting the liquidity of p62/SQSTM1 condensates.Nature communications · 2021Article
- The retinoid X receptor α modulator K-80003 suppresses inflammatory and catabolic responses in a rat model of osteoarthritis.Scientific reports · 2021Article
- Norlichexanthone purified from plant endophyte prevents postmenopausal osteoporosis by targeting ERActa pharmaceutica Sinica. B · 2021Article
- Oncogenic potential of truncated RXRα during colitis-associated colorectal tumorigenesis by promoting IL-6-STAT3 signaling.Nature communications · 2019Article
- Discovery of atorvastatin as a tetramer stabilizer of nuclear receptor RXRα through structure-based virtual screening.Bioorganic chemistry · 2019Article
- Steroids from the Deep-Sea-Derived FungusMarine drugs · 2019Article
- [Research progress on the involvement of nuclear receptor in regulating autophagy].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2018Review
- Overview of the structure-based non-genomic effects of the nuclear receptor RXRα.Cellular & molecular biology letters · 2018Review
Corrections and comments
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Authors and funding
23 authors at 4 institutions in 2 countries.
Funding
Abstract
Retinoid X receptor-alpha (RXRα) binds to DNA either as homodimers or heterodimers, but it also forms homotetramers whose function is poorly defined. We previously discovered that an N-terminally-cleaved form of RXRα (tRXRα), produced in tumour cells, activates phosphoinositide 3-kinase (PI3K) signalling by binding to the p85α subunit of PI3K and that K-80003, an anti-cancer agent, inhibits this process. Here, we report through crystallographic and biochemical studies that K-80003 binds to and stabilizes tRXRα tetramers via a 'three-pronged' combination of canonical and non-canonical mechanisms. K-80003 binding has no effect on tetramerization of RXRα, owing to the head-tail interaction that is absent in tRXRα. We also identify an LxxLL motif in p85α, which binds to the coactivator-binding groove on tRXRα and dissociates from tRXRα upon tRXRα tetramerization. These results identify conformational selection as the mechanism for inhibiting the nongenomic action of tRXRα and provide molecular insights into the development of RXRα cancer therapeutics.
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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.