ArticleProtein science : a publication of the Protein Society2021
DNA-binding domain as the minimal region driving RNA-dependent liquid-liquid phase separation of androgen receptor.
Article in Protein science : a publication of the Protein Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- DNA binding and dimerization of the SOG1 NAC domain are functionally linked with its ability to undergo liquid-liquid phase separation.Nucleic acids research · 2026Article
- The role of LLPS of biomacromolecules in the gonads and related diseases.Frontiers in endocrinology · 2026Review
- Evolving roles for the androgen receptor and its protein interactome in castration-resistant prostate cancer.Oncogene · 2025Review
- Nuclear receptors as novel regulators that modulate cancer radiosensitivity and normal tissue radiotoxicity.Molecular cancer · 2025Review
- Molecular insights into the effect of 1,6-hexanediol on FUS phase separation.The EMBO journal · 2025Article
- Conformational modulation of intrinsically disordered transactivation domains for cancer therapy.PNAS nexus · 2025Review
- Structured protein domains enter the spotlight: modulators of biomolecular condensate form and function.Trends in biochemical sciences · 2025Review
- Article
- The androgen receptor amino-terminal domain: structure, function and therapeutic potential.Endocrine oncology (Bristol, England) · 2025Review
- RNA fine-tunes estrogen receptor-alpha binding on low-affinity DNA motifs for transcriptional regulation.The EMBO journal · 2024Article
- Review
- Phase separation and transcriptional regulation in cancer development.Journal of biomedical research · 2024Article
- Phase separation in gene transcription control.Acta biochimica et biophysica Sinica · 2023Review
- Phase separation propensity of the intrinsically disordered AB region of human RXRβ.Cell communication and signaling : CCS · 2023Article
- A Liquid-Liquid Phase Separation-Related Index Associate with Biochemical Recurrence and Tumor Immune Environment of Prostate Cancer Patients.International journal of molecular sciences · 2023Article
- Dynamic phase separation of the androgen receptor and its coactivators key to regulate gene expression.Nucleic acids research · 2023Article
- Inhibiting androgen receptor splice variants with cysteine-selective irreversible covalent inhibitors to treat prostate cancer.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Liquid‒liquid phase separation: roles and implications in future cancer treatment.International journal of biological sciences · 2023Review
- Phase-separation: a possible new layer for transcriptional regulation by glucocorticoid receptor.Frontiers in endocrinology · 2023Review
- Breaking apart condensates.Nature chemical biology · 2022Article
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Androgen receptor (AR) is a nuclear hormone receptor that regulates the transcription of genes involved in the development of testis, prostate and the nervous system. Misregulation of AR is a major driver of prostate cancer (PC). The primary agonist of full-length AR is testosterone, whereas its splice variants, for example, AR-v7 implicated in cancer may lack a ligand-binding domain and are thus devoid of proper hormonal control. Recently, it was demonstrated that full-length AR, but not AR-v7, can undergo liquid-liquid phase separation (LLPS) in a cellular model of PC. In a detailed bioinformatics and deletion analysis, we have analyzed which AR region is responsible for LLPS. We found that its DNA-binding domain (DBD) can bind RNA and can undergo RNA-dependent LLPS. RNA regulates its LLPS in a reentrant manner, that is, it has an inhibitory effect at higher concentrations. As RNA binds DBD more weakly than DNA, while both RNA and DNA localizes into AR droplets, its LLPS depends on the relative concentration of the two nucleic acids. The region immediately preceding DBD has no effect on the LLPS propensity of AR, whereas the functional part of its long N-terminal disordered transactivation domain termed activation function 1 (AF1) inhibits AR-v7 phase separation. We suggest that the resulting diminished LLPS tendency of AR-v7 may contribute to the misregulation of the transcription function of AR in prostate cancer.
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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.