ArticleNature communications2024
The homeodomain regulates stable DNA binding of prostate cancer target ONECUT2.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Computer-Aided Discovery of EGFR G-Quadruplex Targeting Phenanthroimidazole Derivatives Inducing Concurrent Multi-Organelle Damage in Glioblastoma.Antioxidants (Basel, Switzerland) · 2026Article
- Predicting protein-nucleic acid interactions via protein language models with biophysical and evolutionary priors.iScience · 2026Article
- Molecular mechanisms and classification of castration-resistant prostate cancer: Insights into androgen receptor, cancer stem cells, and neuroendocrine features.Current urology · 2026Article
- Roles of PEG10 in cancer and neurodegenerative disorder (Review).Oncology reports · 2025Review
- Transcriptional Landscape of CUT-Class Homeobox Genes in Blastic Plasmacytoid Dendritic Cell Neoplasm.International journal of molecular sciences · 2024Article
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9 authors.
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Abstract
The CUT and homeodomain are ubiquitous DNA binding elements often tandemly arranged in multiple transcription factor families. However, how the CUT and homeodomain work concertedly to bind DNA remains unknown. Using ONECUT2, a driver and therapeutic target of advanced prostate cancer, we show that while the CUT initiates DNA binding, the homeodomain thermodynamically stabilizes the ONECUT2-DNA complex through allosteric modulation of CUT. We identify an arginine pair in the ONECUT family homeodomain that can adapt to DNA sequence variations. Base interactions by this ONECUT family-specific arginine pair as well as the evolutionarily conserved residues are critical for optimal DNA binding and ONECUT2 transcriptional activity in a prostate cancer model. The evolutionarily conserved base interactions additionally determine the ONECUT2-DNA binding energetics. These findings provide insights into the cooperative DNA binding by CUT-homeodomain proteins.
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