ArticleThe Journal of biological chemistry2015
Structures of the Ets Protein DNA-binding Domains of Transcription Factors Etv1, Etv4, Etv5, and Fev: DETERMINANTS OF DNA BINDING AND REDOX REGULATION BY DISULFIDE BOND FORMATION.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- ETV1 Couples Reciprocal FGF23 and PTH Signaling to RenalResearch square · 2026Article
- Transcriptomic Analysis in the Liver of Two Rabbit Lines Divergently Selected for Intramuscular Fat Content.Animal genetics · 2026Article
- Filamin-ETV4/5 acts as mechanosensor-mechanotransducer axis that drives cell competition-mediated elimination of transformed cells.Nature communications · 2026Article
- An epigenomic investigation of atrial fibrillation in a matched left and right atrial human cohort.Clinical epigenetics · 2026Article
- Emerging role of ETV4 in colorectal cancer: from molecular mechanisms to clinical implications.Frontiers in oncology · 2026Review
- Identification and Validation of Biomarkers to Predict Early Diagnosis of Inflammatory Bowel Disease and Its Progression to Colorectal Cancer.Biochemical genetics · 2025Article
- FLI1 and GATA1 governHaematologica · 2025Article
- Phase separation of the oncogenic fusion protein EWS::FLI1 is modulated by its DNA-binding domain.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Oncogenic Fusions HarboringCancers · 2025Review
- ETV5 reduces androgen receptor expression and induces neural stem-like properties during neuroendocrine prostate cancer development.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structure and cooperative formation of a FLI1 filament on contiguous GGAA DNA sites.Nucleic acids research · 2025Article
- ETVs dictate hPSC differentiation by tuning biophysical properties.Nature communications · 2025Article
- Evidence for Fgf and Wnt regulation ofFrontiers in cell and developmental biology · 2025Article
- Prognostic value ofWorld journal of gastrointestinal oncology · 2024Article
- Article
- Dissolution of oncofusion transcription factor condensates for cancer therapy.Nature chemical biology · 2023Article
- Genetic Study of Elf5 and Ehf in the Mouse Salivary Gland.Journal of dental research · 2023Article
- HBx increases chromatin accessibility and ETV4 expression to regulate dishevelled-2 and promote HCC progression.Cell death & disease · 2022Article
- Allosteric interference in oncogenic FLI1 and ERG transactions by mithramycins.Structure (London, England : 1993) · 2021Article
- Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Ets transcription factors, which share the conserved Ets DNA-binding domain, number nearly 30 members in humans and are particularly involved in developmental processes. Their deregulation following changes in expression, transcriptional activity, or by chromosomal translocation plays a critical role in carcinogenesis. Ets DNA binding, selectivity, and regulation have been extensively studied; however, questions still arise regarding binding specificity outside the core GGA recognition sequence and the mode of action of Ets post-translational modifications. Here, we report the crystal structures of Etv1, Etv4, Etv5, and Fev, alone and in complex with DNA. We identify previously unrecognized features of the protein-DNA interface. Interactions with the DNA backbone account for most of the binding affinity. We describe a highly coordinated network of water molecules acting in base selection upstream of the GGAA core and the structural features that may account for discrimination against methylated cytidine residues. Unexpectedly, all proteins crystallized as disulfide-linked dimers, exhibiting a novel interface (distant to the DNA recognition helix). Homodimers of Etv1, Etv4, and Etv5 could be reduced to monomers, leading to a 40-200-fold increase in DNA binding affinity. Hence, we present the first indication of a redox-dependent regulatory mechanism that may control the activity of this subset of oncogenic Ets transcription factors.
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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 Socratic graph.