ArticleThe Journal of biological chemistry2014
Coregulator control of androgen receptor action by a novel nuclear receptor-binding motif.
Article in The Journal of biological chemistry, 2014. 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, 52 citations in OpenAlex.
- The multimerization pathway of the glucocorticoid receptor.Nucleic acids research · 2025Article
- Bile acids target an exposed cavity in the glucocorticoid receptor modulating receptor self-assembly, chromatin binding and transcriptional activity.bioRxiv : the preprint server for biology · 2025Article
- Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer.Molecular cancer therapeutics · 2024Article
- Characterization of allosteric modulators that disrupt androgen receptor co-activator protein-protein interactions to alter transactivation-Drug leads for metastatic castration resistant prostate cancer.SLAS discovery : advancing life sciences R & D · 2023Article
- The multivalency of the glucocorticoid receptor ligand-binding domain explains its manifold physiological activities.Nucleic acids research · 2022Article
- Review
- Structure-Based Study to Overcome Cross-Reactivity of Novel Androgen Receptor Inhibitors.Cells · 2022Article
- Visualization of the protein-protein interactions of hormone receptors in hormone-dependent cancer research.Endocrine oncology (Bristol, England) · 2022Review
- Epigenetic Coregulation of Androgen Receptor Signaling.Advances in experimental medicine and biology · 2022Article
- Androgen receptor co-regulation in prostate cancer.Asian journal of urology · 2020Review
- Functional Comparison of Human and Zebra Fish FKBP52 Confirms the Importance of the Proline-Rich Loop for Regulation of Steroid Hormone Receptor Activity.International journal of molecular sciences · 2019Article
- Article
- Order in Disorder as Observed by the "Hydrophobic Cluster Analysis" of Protein Sequences.Proteomics · 2018Review
- Selective modulation of the androgen receptor AF2 domain rescues degeneration in spinal bulbar muscular atrophy.Nature medicine · 2018Article
- Development of Bag-1L as a therapeutic target in androgen receptor-dependent prostate cancer.eLife · 2017Article
- Targeting Binding Function-3 of the Androgen Receptor Blocks Its Co-Chaperone Interactions, Nuclear Translocation, and Activation.Molecular cancer therapeutics · 2016Article
- TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer.Cancer cell · 2016Article
- Functional analysis of androgen receptor mutations that confer anti-androgen resistance identified in circulating cell-free DNA from prostate cancer patients.Genome biology · 2016Article
- Antiandrogens act as selective androgen receptor modulators at the proteome level in prostate cancer cells.Molecular & cellular proteomics : MCP · 2015Article
- New Sites for Old Suspects: Environmental Allosteric Modifiers of Nuclear Hormone Receptors.Journal of pharmacology & clinical toxicology · 2015Article
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 3 countries.
Funding
Abstract
The androgen receptor (AR) is a ligand-activated transcription factor that is essential for prostate cancer development. It is activated by androgens through its ligand-binding domain (LBD), which consists predominantly of 11 α-helices. Upon ligand binding, the last helix is reorganized to an agonist conformation termed activator function-2 (AF-2) for coactivator binding. Several coactivators bind to the AF-2 pocket through conserved LXXLL or FXXLF sequences to enhance the activity of the receptor. Recently, a small compound-binding surface adjacent to AF-2 has been identified as an allosteric modulator of the AF-2 activity and is termed binding function-3 (BF-3). However, the role of BF-3 in vivo is currently unknown, and little is understood about what proteins can bind to it. Here we demonstrate that a duplicated GARRPR motif at the N terminus of the cochaperone Bag-1L functions through the BF-3 pocket. These findings are supported by the fact that a selective BF-3 inhibitor or mutations within the BF-3 pocket abolish the interaction between the GARRPR motif(s) and the BF-3. Conversely, amino acid exchanges in the two GARRPR motifs of Bag-1L can impair the interaction between Bag-1L and AR without altering the ability of Bag-1L to bind to chromatin. Furthermore, the mutant Bag-1L increases androgen-dependent activation of a subset of AR targets in a genome-wide transcriptome analysis, demonstrating a repressive function of the GARRPR/BF-3 interaction. We have therefore identified GARRPR as a novel BF-3 regulatory sequence important for fine-tuning the activity of the AR.
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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.