ArticleNucleic acids research2017
Structured and disordered regions cooperatively mediate DNA-binding autoinhibition of ETS factors ETV1, ETV4 and ETV5.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- ETV1/TGF-β/SMAD4-CTGF Axis Activated Tumor-CAFs Crosstalk Promotes Poor Progression in Hepatocellular Carcinoma Patients.Cancer medicine · 2026Article
- Architectural and evolutionary features of TE-derived TSSs shape tissue-specific promoter activity in the human genome.Nature communications · 2026Article
- Article
- Short activation domains control chromatin association of transcription factors.bioRxiv : the preprint server for biology · 2025Article
- Comprehensive analysis of the functional and immunological significance of ETV4 in pan-cancer and its validation in digestive tumors.Frontiers in immunology · 2025Article
- ETV4 interacts with LOXL2 to induce epigenetic activation of NID1 during colorectal cancer progression.International journal of biological sciences · 2025Article
- NMR investigation of FOXO4-DNA interaction for discriminating target and non-target DNA sequences.Communications biology · 2024Article
- Prognostic value ofWorld journal of gastrointestinal oncology · 2024Article
- Autoinhibited Protein Database: a curated database of autoinhibitory domains and their autoinhibition mechanisms.Database : the journal of biological databases and curation · 2024Article
- Co-translational Installation of Posttranslational Modifications by Non-canonical Amino Acid Mutagenesis.Chembiochem : a European journal of chemical biology · 2023Article
- Identification and characterization of novel ETV4 splice variants in prostate cancer.Scientific reports · 2023Article
- E26 transformation-specific transcription variant 5 in development and cancer: modification, regulation and function.Journal of biomedical science · 2023Review
- Connecting sequence features within the disordered C-terminal linker ofProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- E26 transformation-specific variant 4 as a tumor promotor in human cancers through specific molecular mechanisms.Molecular therapy oncolytics · 2021Review
- The human CRY1 tail controls circadian timing by regulating its association with CLOCK:BMAL1.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Asymmetric Conservation within Pairs of Co-Occurred Motifs Mediates Weak Direct Binding of Transcription Factors in ChIP-Seq Data.International journal of molecular sciences · 2020Article
- Intrinsic disorder controls two functionally distinct dimers of the master transcription factor PU.1.Science advances · 2020Article
- Function and regulation of the PEA3 subfamily of ETS transcription factors in cancer.American journal of cancer research · 2020Review
- Intrinsically disordered regions regulate both catalytic and non-catalytic activities of the MutLα mismatch repair complex.Nucleic acids research · 2019Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Autoinhibition enables spatial and temporal regulation of cellular processes by coupling protein activity to surrounding conditions, often via protein partnerships or signaling pathways. We report the molecular basis of DNA-binding autoinhibition of ETS transcription factors ETV1, ETV4 and ETV5, which are often overexpressed in prostate cancer. Inhibitory elements that cooperate to repress DNA binding were identified in regions N- and C-terminal of the ETS domain. Crystal structures of these three factors revealed an α-helix in the C-terminal inhibitory domain that packs against the ETS domain and perturbs the conformation of its DNA-recognition helix. Nuclear magnetic resonance spectroscopy demonstrated that the N-terminal inhibitory domain (NID) is intrinsically disordered, yet utilizes transient intramolecular interactions with the DNA-recognition helix of the ETS domain to mediate autoinhibition. Acetylation of selected lysines within the NID activates DNA binding. This investigation revealed a distinctive mechanism for DNA-binding autoinhibition in the ETV1/4/5 subfamily involving a network of intramolecular interactions not present in other ETS factors. These distinguishing inhibitory elements provide a platform through which cellular triggers, such as protein-protein interactions or post-translational modifications, may specifically regulate the function of these oncogenic proteins.
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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.