ArticleProceedings of the National Academy of Sciences of the United States of America2020
Modulation of androgen receptor DNA binding activity through direct interaction with the ETS transcription factor ERG.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 51 citations in OpenAlex.
- ERG Orchestrates a Dedifferentiation-Senescence-Inflammation Triad in Prostate Cancer.Molecular cancer research : MCR · 2026Article
- Molecular determinants of AR-enhancer interaction and cistrome reprogramming in prostate cancer progression.Endocrine-related cancer · 2026Review
- Review
- Rewiring Oncogenic Transcriptional Complexes with Domain-ALTeration Chimeras (DALTACs) in Prostate Cancer.bioRxiv : the preprint server for biology · 2026Article
- Overexpression of the ERG oncogene in prostate cancer identifies candidates for PARP inhibitor-based radiosensitization.The Journal of clinical investigation · 2026Article
- Androgen deprivation-mediated activation of AKT is enhanced in prostate cancer with TMPRSS2:ERG fusion.The Journal of clinical investigation · 2025Article
- Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer.Nature genetics · 2025Article
- ERG-driven prostate cancer initiation is cell-context dependent and requires KMT2A and DOT1L.Nature genetics · 2025Article
- Polyglutamine expansion induced dynamic misfolding of androgen receptor.Protein science : a publication of the Protein Society · 2025Article
- The Effect of Estradiol and Testosterone Levels Alone or in Combination with Their Receptors in Predicting the Severity of Systemic Lupus Erythematosus: A Cohort Study.Iranian journal of medical sciences · 2025Article
- Coactivator networks orchestrating noncanonical AR programs in enzalutamide-resistant CRPC.Frontiers in oncology · 2025Review
- Review
- Glucocorticoid receptor action in prostate cancer: the role of transcription factor crosstalk.Frontiers in endocrinology · 2024Review
- Statin use and mortality risk in Asian patients with prostate cancer receiving androgen deprivation therapy: A population-based cohort study.Cancer medicine · 2024Article
- ETV4 mediates dosage-dependent prostate tumor initiation and cooperates with p53 loss to generate prostate cancer.Science advances · 2023Article
- Transcriptomes of Prostate Cancer with TMPRSS2:ERG and Other ETS Fusions.Molecular cancer research : MCR · 2023Article
- Structural insights into the HNF4 biology.Frontiers in endocrinology · 2023Review
- Metformin use and mortality in Asian, diabetic patients with prostate cancer on androgen deprivation therapy: A population-based study.The Prostate · 2023Article
- The Association between Cyclin Dependent Kinase 2 Associated Protein 1 (CDK2AP1) and Molecular Subtypes of Lethal Prostate Cancer.International journal of molecular sciences · 2022Article
- Retinoic acid receptor structures: the journey from single domains to full-length complex.Journal of molecular endocrinology · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The androgen receptor (AR) is a type I nuclear hormone receptor and the primary drug target in prostate cancer due to its role as a lineage survival factor in prostate luminal epithelium. In prostate cancer, the AR cistrome is reprogrammed relative to normal prostate epithelium and particularly in cancers driven by oncogenic ETS fusion genes. The molecular basis for this change has remained elusive. Using purified proteins, we report a minimal cell-free system that demonstrates interdomain cooperativity between the ligand (LBD) and DNA binding domains (DBD) of AR, and its autoinhibition by the N terminus of AR. Furthermore, we identify ERG as a cofactor that activates AR's ability to bind DNA in both high and lower affinity contexts through direct interaction within a newly identified AR-interacting motif (AIM) in the ETS domain, independent of ERG's own DNA binding ability. Finally, we present evidence that this interaction is conserved among ETS factors whose expression is altered in prostate cancer. Our work highlights, at a biochemical level, how tumor-initiating ETS translocations result in reprogramming of the AR cistrome.
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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.