ArticleProceedings of the National Academy of Sciences of the United States of America2010
Ras signaling requires dynamic properties of Ets1 for phosphorylation-enhanced binding to coactivator CBP.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Role of the E26 transformation specific transcription factor family in metabolic disorders.Journal of endocrinological investigation · 2025Review
- Enhanced ETS1 stability by DNAPKcs orchestrates transcriptional changes during chemoresistance in triple negative breast cancer.NPJ breast cancer · 2025Article
- The silence within: a conserved intragenic silencing element governs HTLV-1 expression via host RUNX1 complex binding.Npj viruses · 2025Article
- Heme regulates protein interactions and phosphorylation of BACH2 intrinsically disordered region in humoral response.iScience · 2025Article
- ETS-1 in tumor immunology: implications for novel anti-cancer strategies.Frontiers in immunology · 2025Review
- LILRB1-HLA-G axis defines a checkpoint driving natural killer cell exhaustion in tuberculosis.EMBO molecular medicine · 2024Article
- ETS1 Function in Leukemia and Lymphoma.Advances in experimental medicine and biology · 2024Review
- The roles of ETS transcription factors in liver fibrosis.Human cell · 2023Review
- Loss of CRY2 promotes regenerative myogenesis by enhancing PAX7 expression and satellite cell proliferation.MedComm · 2023Article
- ETS1-HMGA2 Axis Promotes Human Limbal Epithelial Stem Cell Proliferation.Investigative ophthalmology & visual science · 2023Article
- Balanced Force Field ff03CMAP Improving the Dynamics Conformation Sampling of Phosphorylation Site.International journal of molecular sciences · 2022Article
- Ets1 functions partially redundantly with Etv2 to promote embryonic vasculogenesis and angiogenesis in zebrafish.Developmental biology · 2020Article
- Cordycepin Resensitizes T24R2 Cisplatin-Resistant Human Bladder Cancer Cells to Cisplatin by Inactivating Ets-1 Dependent MDR1 Transcription.International journal of molecular sciences · 2020Article
- The E-Twenty-Six Family in Hepatocellular Carcinoma: Moving into the Spotlight.Frontiers in oncology · 2020Review
- Regulation of cisplatin-resistant head and neck squamous cell carcinoma by the SRC/ETS-1 signaling pathway.BMC cancer · 2019Article
- Article
- Specification and formation of the neural crest: Perspectives on lineage segregation.Genesis (New York, N.Y. : 2000) · 2019Review
- Transcription Factor ETS-1 and Reactive Oxygen Species: Role in Vascular and Renal Injury.Antioxidants (Basel, Switzerland) · 2018Review
- Electrostatic Interactions in Protein Structure, Folding, Binding, and Condensation.Chemical reviews · 2018Review
- Aberrant expression of ETS1 and ETS2 proteins in cancer.Cancer reports and reviews · 2018Article
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Authors and funding
7 authors.
Funding
Abstract
Ras/MAPK signaling is often aberrantly activated in human cancers. The downstream effectors are transcription factors, including those encoded by the ETS gene family. Using cell-based assays and biophysical measurements, we have determined the mechanism by which Ras/MAPK signaling affects the function of Ets1 via phosphorylation of Thr38 and Ser41. These ERK2 phosphoacceptors lie within the unstructured N-terminal region of Ets1, immediately adjacent to the PNT domain. NMR spectroscopic analyses demonstrated that the PNT domain is a four-helix bundle (H2-H5), resembling the SAM domain, appended with two additional helices (H0-H1). Phosphorylation shifted a conformational equilibrium, displacing the dynamic helix H0 from the core bundle. The affinity of Ets1 for the TAZ1 (or CH1) domain of the coactivator CBP was enhanced 34-fold by phosphorylation, and this binding was sensitive to ionic strength. NMR-monitored titration experiments mapped the interaction surfaces of the TAZ1 domain and Ets1, the latter encompassing both the phosphoacceptors and PNT domain. Charge complementarity of these surfaces indicate that electrostatic forces act in concert with a conformational equilibrium to mediate phosphorylation effects. We conclude that the dynamic helical elements of Ets1, appended to a conserved structural core, constitute a phospho-switch that directs Ras/MAPK signaling to downstream changes in gene expression. This detailed structural and mechanistic information will guide strategies for targeting ETS proteins in human disease.
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