Affinage

ETS1

Protein C-ets-1 · UniProt P14921

Length
441 aa
Mass
50.4 kDa
Annotated
2026-06-09
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ETS1 is a sequence-specific transcription factor, the mammalian ortholog of the avian v-ets oncogene, that integrates signaling inputs to control gene programs governing lymphocyte development, vascular biology, and tumor invasion (PMID:2847145, PMID:7566177, PMID:7566176). Its DNA-binding activity is gated by an autoinhibitory module in which marginally stable N-terminal helices (HI-1, HI-2) pack against C-terminal inhibitory sequences and the ETS domain, an arrangement whose lability allows allosteric coupling of DNA binding to conformational change (PMID:15591056); multi-site phosphorylation of a flexible serine-rich region in response to Ca2+ signaling stabilizes this inhibited conformation through transient intramolecular contacts with the DNA-binding interface (PMID:18692067). Activating inputs converge through the unstructured N-terminal tail and adjacent PNT domain: ERK2 docks on this region and phosphorylates Thr-38, and MAPK phosphorylation enhances transactivation by promoting preferential recruitment of the CBP/p300 coactivators (PMID:17105191, PMID:15572696). ETS1 is further controlled post-translationally by repressive sumoylation at K15/K227, by K48-linked polyubiquitination and proteasomal degradation, and by counteracting stabilization via the deubiquitinase Usp9x (PMID:16862185, PMID:28198367). Autoinhibition is relieved cooperatively through partnership with core binding factor/AML1, which contacts both the exon VII inhibitory domain and the ETS domain to reciprocally stimulate DNA binding on the TCRβ enhancer (PMID:8264651, PMID:10075931). ETS1 binds an extensive set of co-regulators that tune its output, including repressors (MafB, Daxx, EAPII, HDAC1, Blimp-1) and coactivators (Sp100, nuclear receptors), and drives invasion and angiogenesis genes such as uPA, MMP-9, and GATA-2 (PMID:8620536, PMID:9528793, PMID:9639404, PMID:16294212). In T cells ETS1 maintains survival and supports Treg/Foxp3 development and IL-2 production by facilitating NFAT nuclear entry, while in B cells it restrains plasmacytic differentiation by blocking Blimp-1 DNA binding (PMID:7566177, PMID:7566176, PMID:20855499, PMID:24019486, PMID:17977828). In endothelial cells, VEGF-stimulated acetylation enhances ETS1 chromatin occupancy and BRD4 binding to broadly promote RNAPII pause release and angiogenesis, and ETS1 cooperates with GATA4 to direct lineage-selective enhancer activation (PMID:28851877, PMID:36263775).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1988 High

    Establishing that the human gene encodes the mammalian ortholog of the v-ets oncogene defined ETS1 as a protooncogene-derived transcription factor worth dissecting mechanistically.

    Evidence cDNA sequencing and ORF analysis of human ETS1 versus chicken c-ets-1

    PMID:2847145

    Open questions at the time
    • Sequence alone did not define DNA-binding specificity or regulatory mechanism
    • No isoform or subcellular complexity addressed
  2. 1990 High

    Demonstrating multiple isoforms arising from splicing and phosphorylation, with distinct subcellular distributions, revealed that ETS1 activity is regulated at the level of protein form and localization.

    Evidence Monoclonal antibodies, subcellular fractionation, PCR and exon-specific antibodies

    PMID:2189104

    Open questions at the time
    • Functional consequences of isoform differences not resolved
    • Kinases responsible for phosphorylation not identified
  3. 1992 Medium

    Mapping AP-1-responsive and autoregulatory elements in the ETS1 promoter showed how ETS1 expression is itself wired into mitogenic signaling and positive feedback.

    Evidence Promoter cloning, deletion analysis and reporter transfection assays

    PMID:1614856 PMID:1945412

    Open questions at the time
    • Reporter-based, single-lab evidence
    • Endogenous chromatin context not tested
  4. 1994 High

    Reconstitution of an ETS1-CBF ternary complex on the TCRβ enhancer established cooperative DNA binding as a core mechanism for ETS1 target selection.

    Evidence Recombinant protein binding, EMSA, oligonucleotide mutagenesis and binding kinetics

    PMID:8264651

    Open questions at the time
    • Structural basis of cooperativity not yet defined
    • Whether autoinhibition is relieved by CBF not addressed here
  5. 1995 High

    Knockout mice defined the physiological requirement for ETS1 in T cell survival/activation and in restraining terminal B cell differentiation, linking the transcription factor to lymphocyte biology.

    Evidence Blastocyst complementation, ES-cell gene targeting, flow cytometry, proliferation and apoptosis assays (two independent labs)

    PMID:7566176 PMID:7566177

    Open questions at the time
    • Direct target genes mediating the phenotypes not identified
    • Molecular mechanism of B cell restraint unknown at this stage
  6. 1998 High

    Identifying CBP/p300 binding and the NMR structure of the PNT domain showed that ETS1 transactivation operates via coactivator recruitment through a protein-interaction module, not the DNA-binding domain.

    Evidence Co-IP, GST pulldown, HAT assays, reporters; NMR structure of a PNT-domain fragment

    PMID:9528793 PMID:9770451

    Open questions at the time
    • How phosphorylation modulates CBP recruitment not yet established
    • PNT-domain partners beyond CBP/p300 unknown
  7. 1999 High

    Mapping the dual ETS1-AML1 contact points demonstrated mutual relief of autoinhibition as the mechanistic basis of cooperative transactivation.

    Evidence Co-IP, domain-deletion mapping, dominant-negative mutants, EMSA, reporter assays

    PMID:10075931

    Open questions at the time
    • Atomic structure of the autoinhibited state not yet resolved
    • Generality across other ETS1 partners not tested
  8. 2002 Medium

    Discovery of repressive (MafB, Daxx, EAPII) and coactivating (Sp100) interactors, together with target promoters (uPA, MMP-9, MMP1), built the picture of ETS1 as a hub for context-dependent co-regulator control of invasion genes.

    Evidence Yeast hybrid screens, GST pulldown, Co-IP, reporter and migration assays

    PMID:10698492 PMID:11909962 PMID:12743594 PMID:8620536 PMID:9639404

    Open questions at the time
    • Many interactions rest on single-lab Co-IP/reporter data
    • Endogenous co-occupancy on chromatin not demonstrated
  9. 2004 High

    Structural and biochemical dissection of the autoinhibitory module, ERK2 docking/Thr-38 phosphorylation, and phosphorylation-enhanced CBP/p300 recruitment defined the allosteric logic linking signaling to ETS1 output.

    Evidence NMR with relaxation/hydrogen exchange; in vitro kinase, fluorescence anisotropy, affinity chromatography, Co-IP and reporters

    PMID:15572696 PMID:15591056 PMID:17105191

    Open questions at the time
    • In vivo dynamics of autoinhibition during signaling not directly measured
    • Quantitative contribution of each PTM in cells unresolved
  10. 2006 High

    Identification of sumoylation, polyubiquitination/proteasomal degradation, and SUMO-pathway enzymes established post-translational turnover and SUMO marking as repressive controls on ETS1 abundance and activity.

    Evidence K→R mutagenesis, SUMO-pathway co-transfection, reporter assays, proteasome inhibition, Co-IP

    PMID:16729975 PMID:16862185

    Open questions at the time
    • Physiological signals triggering sumoylation not defined
    • Identity of the responsible ubiquitin ligase not established
  11. 2008 High

    NMR/PRE analysis of serine-rich-region phosphorylation, the crystal structure of DNA-dependent homodimerization, and the GATA-2 regulatory axis linked Ca2+ signaling, DNA architecture, and hematopoietic lineage choice to ETS1 conformation.

    Evidence NMR with PRE, denaturation and DNA-binding assays; X-ray crystallography, EMSA, ChIP and reporters

    PMID:16294212 PMID:18566588 PMID:18692067

    Open questions at the time
    • In vivo prevalence of the homodimeric mode unquantified
    • Cross-talk between SRR phosphorylation and partner binding not fully mapped
  12. 2013 High

    T-cell studies showed ETS1 acts through partner transcription factors—as a T-bet cofactor, an HDAC1-recruiting IL-10 repressor, a Foxp3-enhancer-occupying Treg determinant, and an NFAT nuclear-entry facilitator—explaining its immunological phenotypes mechanistically.

    Evidence KO mice, ChIP, Co-IP, subcellular fractionation, suppression and cytokine assays

    PMID:15728239 PMID:17977828 PMID:20855499 PMID:22266280 PMID:24019486

    Open questions at the time
    • How a single factor coordinates opposing activating/repressive roles unresolved
    • Direct structural basis of NFAT/Blimp-1 binding not defined
  13. 2017 High

    VEGF-induced acetylation coupling ETS1 to BRD4 and RNAPII pause release, and Usp9x-mediated stabilization driving NRAS in melanoma, revealed acetylation and deubiquitination as activating switches controlling angiogenic and oncogenic programs.

    Evidence ChIP-seq, Co-IP, acetylation/ubiquitination assays, knockdown, in vitro and in vivo angiogenesis and tumor models

    PMID:28198367 PMID:28851877

    Open questions at the time
    • Acetyltransferase responsible for ETS1 acetylation not identified
    • Generality of pause-release mechanism beyond endothelium untested
  14. 2022 High

    Demonstrating that ETS1 redirects GATA4 pioneer binding to open lineage-selective enhancers showed ETS1 functions as a partner that shapes chromatin accessibility for tissue-specific gene programs.

    Evidence Co-IP, lineage-specific ChIP, ATAC-seq, scRNA-seq, reporter assays

    PMID:36263775

    Open questions at the time
    • Mechanism by which ETS1 biases pioneer binding not resolved
    • Whether this cooperativity generalizes to other pioneer factors unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many regulatory layers—autoinhibition, multi-site phosphorylation, sumoylation, ubiquitination, acetylation, and dozens of partner interactions—are integrated in vivo to specify a given ETS1 target program in a given cell type remains unresolved.
  • No unified model linking PTM state to genome-wide occupancy
  • Stoichiometry and temporal order of competing partner interactions unknown
  • Acetyltransferase and ubiquitin ligase identities incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 2
Partners
BRD4CREBBPDAXXEP300GATA4MAFBNFATRUNX1

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 Human ETS1 encodes a protein of 441 amino acids that is >95% identical to chicken c-ets-1, establishing it as the mammalian ortholog of the v-ets oncogene protooncogene transduced by avian leukemia virus E26. cDNA sequencing and open reading frame analysis Proceedings of the National Academy of Sciences of the United States of America High 2847145
1990 The human ets-1 gene produces multiple protein isoforms (p51, p48, p42, p39) by at least two mechanisms: alternative splicing of exon VII and protein phosphorylation; phosphorylated forms (pp52, pp49) are found mainly in the cytoplasm, while p48 and p39 (lacking exon VII) are found mainly in the nucleus. Monoclonal antibody characterization, subcellular fractionation, PCR, and exon-specific antibodies Oncogene High 2189104
1991 The ets-1 promoter contains AP1, AP2, Sp1, and ets-1 binding sites; c-Jun enhances ets-1 promoter activity, and ets-1 positively autoregulates its own expression via an ets-binding site in its promoter. Promoter cloning, reporter transfection assays, sequence analysis Oncogene Medium 1945412
1992 The ets-1 promoter is inducible by serum and by co-expression of c-Fos and c-Jun (AP-1); a 50-bp element containing AP-1 and Ets-1 binding motifs is sufficient for this responsiveness, and Ets-1 positively autoregulates its own promoter. Promoter cloning, deletion analysis, reporter transfection assays Nucleic acids research Medium 1614856
1994 Ets-1 and core binding factor (CBF) form a high-affinity ternary DNA-binding complex on the TCRβ enhancer elements beta E2 and beta E3; CBF-Ets-1-DNA complexes increase Ets-1 DNA binding affinity and decrease CBF dissociation rate; this interaction does not require fixed spacing or orientation of Ets and CBF sites. Recombinant protein binding, electrophoretic mobility shift assay (EMSA), oligonucleotide mutagenesis, binding site selection Molecular and cellular biology High 8264651
1995 Ets-1 is required for normal survival and activation of murine T cells; Ets-1-/- T cells show markedly decreased numbers of mature thymocytes and peripheral T cells, exhibit a severe proliferative defect in response to multiple activating signals, and display increased spontaneous apoptosis in vitro. RAG-2-/- blastocyst complementation, embryonic stem cell gene targeting (homozygous deletion), flow cytometry, proliferation and apoptosis assays Nature High 7566176 7566177
1995 Ets-1 deficiency causes increased T cell apoptosis and abnormally elevated terminal B cell differentiation to IgM-secreting plasma cells; Ets-1-/- T cells are present in reduced numbers and highly susceptible to cell death, while Ets-1-/- B cells are present in normal numbers but a high proportion become IgM plasma cells. RAG-2-deficient blastocyst complementation, gene targeting, flow cytometry, in vitro culture assays Nature High 7566176 7566177
1995 Ets-1 phosphorylation in astrocytes is stimulated by neurotransmitters (bradykinin, carbachol, glutamate, norepinephrine) and is blocked by KT5926 (a myosin light-chain kinase inhibitor), implicating MLCK in ets-1 phosphorylation in vivo. Metabolic labeling, immunoprecipitation, pharmacological inhibition in primary astrocyte cultures and astrocytoma cell lines Molecular and cellular biology Medium 7823957
1996 MafB, an AP-1-like protein expressed in myelomonocytic cells, is a direct interaction partner of Ets-1 that binds to the Ets-1 DNA-binding domain via its basic region/leucine-zipper; MafB represses Ets-1 transactivation of synthetic Ets-binding-site promoters and of the transferrin receptor promoter, thereby inhibiting Ets-1-mediated erythroid differentiation. Yeast one-hybrid screen with DNA-bound Ets-1, domain mapping, reporter transfection, overexpression in erythroblast cell line Cell High 8620536
1998 Ets-1 binds the transcriptional coactivators CBP and p300 through N-terminal cysteine/histidine-rich regions of CBP (residues 313–452 and 1449–1892); this interaction is required for specific Ets-1 transactivation functions; the Ets-1–CBP/p300 immunocomplex possesses histone acetyltransferase activity; E1A (a CBP/p300 inhibitor) represses Ets-1-dependent promoters. Co-immunoprecipitation, GST pulldown, reporter transfection, overexpression, histone acetyltransferase assay Molecular and cellular biology High 9528793
1998 The Ets-1 PNT (Pointed) domain forms a monomeric five-helix bundle (solved by NMR); the MAP kinase phosphorylation site (Thr-38 region) is in a highly flexible, unstructured region that is not structurally altered upon phosphorylation; these findings suggest the PNT domain functions in heterotypic protein–protein interactions rather than DNA binding. NMR structure determination of a 110-residue fragment of murine Ets-1 Proceedings of the National Academy of Sciences of the United States of America High 9770451
1998 Ets-1 and Ets-2 activate the uPA and MMP-9 promoters in response to EGF; activation requires composite Ets and AP-1 binding sites; overexpression of Ets-1/Ets-2 potentiates EGF-induced uPA and MMP-9 promoter activity in ErbB-2-overexpressing breast cancer cells. Reporter transfection assays, expression vector transfection, promoter mutagenesis International journal of cancer Medium 9639404
1999 Ets-1 and AML1 (CBFα/PEBP2αB1) directly interact via two contact points: (1) the autoinhibitory exon VII domain of Ets-1 with the NRDB of AML1, and (2) the DNA-binding domains; this interaction reciprocally relieves autoinhibition of both proteins and stimulates their DNA binding and transactivation cooperatively on the TCRβ enhancer. Co-immunoprecipitation, domain-deletion mapping, dominant-negative mutants, EMSA, reporter transactivation assays The EMBO journal High 10075931
2000 ETS1 interacts with the Daxx protein (EAP1/Daxx) via the ETS1 N-terminal 139 amino acids (Daxx Interaction Domain) and the C-terminal 173 amino acids of Daxx; this interaction represses ETS1-mediated transcriptional activation of MMP1 and BCL2 genes; both interaction domains are required for repression. Yeast two-hybrid screen, in vitro pulldown, nuclear co-localization, co-transfection reporter assays, domain deletion Oncogene Medium 10698492
2000 Ets-1 interacts directly with vitamin D receptor (VDR), estrogen receptor (ER), and PPARα via their respective DNA-binding domains; this interaction induces a conformational change in VDR (increased protease resistance) and enables ligand-independent, AF2-independent transcriptional activation of these nuclear receptors, as well as recruitment of coactivators to AF2-deficient mutant receptors. Co-immunoprecipitation, GST pulldown, reporter assays, limited proteolysis, domain mutagenesis Molecular and cellular biology High 11073980
2001 Hypoxia induces ETS-1 expression via HIF-1: deletion of a region between -424 and -279 bp of the ETS-1 promoter reduces hypoxia-mediated inducibility; HIF-1 binds to a hypoxia responsive element-like sequence in this region under hypoxic conditions; decoy oligonucleotides of this sequence inhibit hypoxia-mediated ETS-1 induction. Promoter deletion analysis, EMSA with HIF-1, decoy oligonucleotide experiments, reporter assays Biochemical and biophysical research communications Medium 11708773
2002 Sp100 physically interacts with two regions of ETS-1 (domains A+B and D+E+F) and acts as a coactivator that strongly potentiates ETS-1 transcriptional activation of natural and Ets-focused promoters; ETS-1 overexpression alters nuclear body morphology by recruiting Sp100 away from PML nuclear bodies. Co-immunoprecipitation, GST pulldown, reporter assays, indirect immunofluorescence Molecular and cellular biology Medium 11909962
2003 EAPII interacts with ETS1 (and ETS2, FLI1) both in vitro and in vivo; EAPII is predominantly nuclear; EAPII negatively modulates ETS1 transcriptional activity, attenuates synergistic transactivation by ETS1 and AP-1, and re-expression of EAPII inhibits migration of epithelial cancer cells. Yeast two-hybrid, in vitro pulldown, co-immunoprecipitation, indirect immunofluorescence, reporter assays, migration assay Oncogene Medium 12743594
2004 The autoinhibitory module of Ets-1 is formed by hydrophobic packing of N-terminal inhibitory helices (HI-1, HI-2) with C-terminal inhibitory sequences (H4, H5) and H1 of the ETS domain; HI-1 is only marginally stable (amide exchange ~15-fold slower than unfolded), and this lability enables allosteric coupling of DNA binding with HI-1 unfolding; this mechanism allows modulation of Ets-1 activity by protein partnerships, PTMs, or mutations. NMR spectroscopy, 15N relaxation studies, hydrogen exchange measurements, structure determination The Journal of biological chemistry High 15591056
2004 ERK2 phosphorylates Ets-1 specifically at Thr-38 within the consensus 36ΦχTPro39 sequence; the Ets-1 N-terminal tail contains a previously unrecognized docking site for ERK2 that promotes Thr-38 phosphorylation while discriminating against phosphorylation of Ser-26; Ets-1 engages both the D-recruitment site and F-recruitment site of ERK2. Fluorescence anisotropy binding assays, mutagenesis and truncation analysis, peptide displacement, in vitro phosphorylation Biochemistry High 17105191
2004 MAPK phosphorylation of Ets-1 and Ets-2 at a conserved site N-terminal to the PNT domain results in enhanced transactivation via preferential recruitment of CBP and p300 coactivators; both the phosphoacceptor site (in unstructured region) and the PNT domain are required for this phosphorylation-augmented interaction; CBP and Ets-2 interact in a phosphorylation-enhanced manner in vivo. Affinity chromatography screen of HeLa nuclear extracts, purified protein binding assays, reporter transactivation assays, co-immunoprecipitation Molecular and cellular biology High 15572696
2005 Ets-1 is required for T-bet to promote IFN-γ production in Th1 cells; Ets-1-deficient Th1 cells fail to mount effective Th1 inflammatory responses in vivo and produce abnormally high IL-10; Ets-1 acts as a functional cofactor of T-bet. Ets-1 knockout mouse, in vitro Th1 differentiation, cytokine measurement, in vivo infection model The Journal of experimental medicine High 15728239
2005 Ets-1 is a critical transcriptional mediator of Ang II-mediated vascular inflammation and remodeling; Ets1-/- mice show significantly diminished arterial wall thickening, perivascular fibrosis, and cardiac hypertrophy in response to Ang II; Ets-1 target genes p21CIP, PAI-1, and MCP-1 are identified as downstream mediators; MCP-1 is a novel Ets-1 target whose reduced expression leads to diminished T cell and macrophage recruitment to the vessel wall. Ets-1 knockout mouse, Ang II infusion model, target gene analysis, immunohistochemistry The Journal of clinical investigation High 16138193
2006 Ets-1 is modified by sumoylation at lysines K15 and K227 within synergy control motifs; the E2 SUMO-conjugating enzyme Ubc9 and E3 SUMO ligase PIASy enhance sumoylation, while SUMO protease SENP1 desumoylates Ets-1; sumoylation represses Ets-1 transcriptional activity; Ets-1 is also modified by K48-linked polyubiquitination and degraded via the 26S proteasome, independently of sumoylation sites. Mutagenesis (K→R substitutions), co-transfection with SUMO pathway components, reporter assays, proteasome inhibitor treatment Oncogene High 16862185
2006 PIASy is a specific SUMO-E3 ligase for Ets-1 and a novel interaction partner; PIASy represses Ets-1-dependent transcription independently of Ets-1 sumoylation status (requiring instead sumoylation of other factors). In vivo and in vitro sumoylation assays, mutagenesis, co-immunoprecipitation, reporter assays Biochemical and biophysical research communications Medium 16729975
2007 Ets-1 physically interacts with Blimp-1 and blocks Blimp-1 DNA binding activity and its ability to repress target genes (without affecting Blimp-1 protein levels), thereby limiting plasmacytic differentiation downstream of TLR9; Ets-1 also induces expression of Blimp-1 target genes including Pax-5. Co-immunoprecipitation, EMSA (DNA binding inhibition), reporter assays, gene expression analysis in KO B cells The Journal of biological chemistry High 17977828
2008 Ets-1 DNA-binding affinity is allosterically regulated by a serine-rich region (SRR); multi-site phosphorylation of the flexible SRR in response to Ca2+ signaling enhances thermodynamic stability of the ETS domain and its inhibitory module and shifts Ets-1 to an inhibited conformation via transient intramolecular interactions between the SRR and the DNA-binding interface; paramagnetic relaxation enhancement NMR identified a preferential interaction surface. NMR spectroscopy (including paramagnetic relaxation enhancement), thermal/urea denaturation, DNA binding assays Journal of molecular biology High 18692067
2008 Ets-1 forms a regulated homodimer on the stromelysin-1 promoter palindromic ETS-binding sites; the crystal structure of Ets-1 on this element reveals that homodimerization is mediated by the specific arrangement of two ETS-binding sites and requires the N-terminal flanking region; Ets-1 variants with mutations in this region lose the ability to dimerize on DNA and to transactivate the stromelysin-1 promoter. X-ray crystal structure determination, mutagenesis, EMSA, reporter transactivation assays The EMBO journal High 18566588
2008 In erythroid cells, Ets-1 is downregulated and exported from the nucleus via a leucine-rich nuclear export signal during differentiation; in megakaryocytes, Ets-1 remains nuclear; Ets-1 overexpression blocks erythroid maturation, upregulates GATA-2, and downregulates GATA-1; Ets-1 directly binds to and activates the GATA-2 promoter in vitro and in vivo. Nuclear export signal identification, subcellular fractionation, ChIP, reporter assays, overexpression in CD34+ progenitor cells Cell death and differentiation High 16294212
2010 Ets-1 is required for the development and suppressive function of natural regulatory T cells (Tregs); Ets-1-/- mice develop T cell-mediated autoimmunity with reduced Treg numbers; Ets-1-/- Tregs express low Foxp3 and show decreased in vitro suppression; Ets-1 interacts with the Foxp3 intronic enhancer and is required for demethylation of this regulatory sequence. Ets-1 knockout mouse, RAG2-/- reconstitution chimeras, fetal thymic organ culture, ChIP (Foxp3 enhancer), in vitro suppression assay, IBD transfer model The Journal of experimental medicine High 20855499
2010 Ets-1 and Ets-2 regulate miR-126 expression in endothelial cells; a genomic region (-71 to -100 bp upstream of the miR-126 transcriptional start site) containing an Ets binding site is critical for transactivation; mutations in the Ets binding site block transactivation; knockdown of Ets-1 and Ets-2 decreases miR-126 expression. Reporter assays with promoter deletion/mutagenesis, ChIP, Ets-1/Ets-2 knockdown Arteriosclerosis, thrombosis, and vascular biology Medium 20671229
2012 Ets-1 interacts with HDAC1; co-expression of Ets-1 with HDAC1 synergistically represses IL-10 transcription in Th1 cells; Ets-1 deficiency leads to increased histone H3 acetylation and reduced HDAC1 enrichment at Il10 regulatory regions. Co-immunoprecipitation (physical interaction), chromatin immunoprecipitation (HDAC1 enrichment, H3 acetylation), reporter assays, Ets-1 KO Th1 cells Journal of immunology High 22266280
2012 ETS1 directly activates expression of ATXN2 by binding to an ETS-binding site in the ATXN2 promoter; endogenous ETS1 occupies the ATXN2 promoter (confirmed by supershift EMSA and ChIP); ETS1 overexpression increases ATXN2 expression, deletion of the ETS1-binding site abrogates this effect, and dominant-negative ETS1 or ETS1 shRNA reduce ATXN2 expression. EMSA with supershift assay, ChIP, luciferase reporter assays with promoter deletion, overexpression and dominant-negative/shRNA knockdown Human molecular genetics High 22914732
2013 Ets-1 physically and functionally interacts with NFAT proteins; Ets-1 is required for the recruitment of NFAT to the IL-2 promoter; nuclear Ets-1 exits the nucleus in response to calcium-dependent signals and competes with NFAT for binding to components of the NRON complex (a cytoplasmic trap for phosphorylated NFAT), thereby facilitating NFAT nuclear entry; Ets-1 deficiency impairs nuclear entry but not dephosphorylation of NFAT. Co-immunoprecipitation, ChIP (NFAT recruitment to IL-2 promoter), subcellular fractionation, nuclear entry assays in Ets-1-/- T cells Proceedings of the National Academy of Sciences of the United States of America High 24019486
2017 VEGF stimulates ETS1 acetylation in endothelial cells; acetylated ETS1 has enhanced chromatin occupancy and binds BRD4, which recruits the RNAPII pause-release machinery to broadly increase RNAPII pause release at transcribed genes; this ETS1-BRD4 axis is required for endothelial cell angiogenic responses in vitro and in vivo. ChIP-seq, Co-immunoprecipitation, acetylation assays, dominant-negative and knockdown experiments, in vitro angiogenesis assays, in vivo angiogenesis models Nature communications High 28851877
2017 The deubiquitinating enzyme Usp9x stabilizes Ets-1 by blocking its proteasomal destruction; Usp9x knockdown or inhibition reduces Ets-1 levels and suppresses Ets-1-driven NRAS expression and melanoma tumorigenicity; Usp9x and Ets-1 levels are coincidently elevated in metastatic melanoma. Ubiquitination assays, Usp9x knockdown/inhibition, Co-immunoprecipitation, gene expression analysis, in vivo tumor models Nature communications High 28198367
2019 ETS-1 directly binds to p-Smad3 and prevents its ubiquitination and proteasomal degradation, thereby enhancing TGF-β1/Smad3 signaling and promoting hepatocyte apoptosis; TGF-β1 induces Ets-1 expression through p-Smad2/3 binding to the Ets-1 promoter. Co-immunoprecipitation, ubiquitination assays, promoter binding analysis (ChIP for p-Smad2/3 at Ets-1 promoter), Ets-1 knockdown in primary hepatocytes and NASH mouse model Cell death & disease Medium 31189885
2019 Endothelial-specific deletion of Ets-1 attenuates Ang II-induced cardiac fibrosis by inhibiting endothelial-to-mesenchymal transition (EndMT); Ets-1 knockdown in H5V cells blocks TGF-β1-induced EndMT with decreased expression of Snail, Slug, Twist, and ZEB1. Endothelial-specific conditional Ets-1 knockout mouse, Ang II infusion model, in vitro Ets-1 knockdown with EndMT markers BMB reports Medium 30670148
2021 EHF (ETS homologous factor) suppresses cancer progression by inhibiting ETS1-mediated activation of ZEB1 and ZEB2 expression; specifically, EHF-SF (short form) abrogates ETS1-mediated ZEB1 promoter activation by promoting ETS1 protein degradation. Reporter assays (ZEB1 promoter), EHF overexpression, ETS1 protein level analysis, in vivo xenograft metastasis model Oncogenesis Medium 33712555
2022 GATA4 and ETS1 physically interact (Co-IP) and co-operatively stimulate endothelial cell enhancer activity in reporter assays; ETS1 re-directs GATA4 pioneer binding to endothelial-selective genomic regions and augments GATA4's ability to open previously inaccessible chromatin; ETS1 is enriched at endothelial-selective GATA4-occupied enhancers adjacent to endocardial genes regulated by GATA4. Co-immunoprecipitation, lineage-specific ChIP (biotin-GATA4), ATAC-seq, single-cell RNA-seq, luciferase reporter assays Circulation research High 36263775
2004 STAT6 and Ets-1 form a stable complex that modulates IL-4-induced Socs-1 expression in keratinocytes; co-expression of Ets-1 with STAT6 activation strongly inhibits Socs-1 promoter-luciferase reporter activity; a composite element with STAT6 and Ets binding sequences is required for IL-4 responsiveness. Co-immunoprecipitation (physical interaction), promoter deletion/mutagenesis, reporter assays The Journal of biological chemistry Medium 15199062

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 The biology of the Ets1 proto-oncogene. Molecular cancer 414 12971829
1995 Defective activation and survival of T cells lacking the Ets-1 transcription factor. Nature 320 7566177
1988 Mammalian ets-1 and ets-2 genes encode highly conserved proteins. Proceedings of the National Academy of Sciences of the United States of America 303 2847145
1995 Increased T-cell apoptosis and terminal B-cell differentiation induced by inactivation of the Ets-1 proto-oncogene. Nature 298 7566176
1996 MafB is an interaction partner and repressor of Ets-1 that inhibits erythroid differentiation. Cell 255 8620536
1999 Mutual activation of Ets-1 and AML1 DNA binding by direct interaction of their autoinhibitory domains. The EMBO journal 206 10075931
1994 Cooperative binding of Ets-1 and core binding factor to DNA. Molecular and cellular biology 204 8264651
1998 The Ets-1 and Ets-2 transcription factors activate the promoters for invasion-associated urokinase and collagenase genes in response to epidermal growth factor. International journal of cancer 194 9639404
1994 Differential expression of ets-1 and ets-2 proto-oncogenes during murine embryogenesis. Oncogene 191 8183549
2005 Ets-1 is a critical regulator of Ang II-mediated vascular inflammation and remodeling. The Journal of clinical investigation 190 16138193
1998 A role for CREB binding protein and p300 transcriptional coactivators in Ets-1 transactivation functions. Molecular and cellular biology 180 9528793
2004 Ras/mitogen-activated protein kinase signaling activates Ets-1 and Ets-2 by CBP/p300 recruitment. Molecular and cellular biology 172 15572696
2000 EAP1/Daxx interacts with ETS1 and represses transcriptional activation of ETS1 target genes. Oncogene 157 10698492
2001 Hypoxia induces transcription factor ETS-1 via the activity of hypoxia-inducible factor-1. Biochemical and biophysical research communications 137 11708773
2010 Ets-1 and Ets-2 regulate the expression of microRNA-126 in endothelial cells. Arteriosclerosis, thrombosis, and vascular biology 131 20671229
1990 Isoforms of the human ets-1 protein: generation by alternative splicing and differential phosphorylation. Oncogene 130 2189104
1998 Structure of the Ets-1 pointed domain and mitogen-activated protein kinase phosphorylation site. Proceedings of the National Academy of Sciences of the United States of America 126 9770451
2010 The Ets-1 transcription factor controls the development and function of natural regulatory T cells. The Journal of experimental medicine 108 20855499
2005 Ets-1, a functional cofactor of T-bet, is essential for Th1 inflammatory responses. The Journal of experimental medicine 105 15728239
2017 VEGF amplifies transcription through ETS1 acetylation to enable angiogenesis. Nature communications 103 28851877
2005 Ets-1 deficiency leads to altered B cell differentiation, hyperresponsiveness to TLR9 and autoimmune disease. International immunology 101 16051621
1996 Expression of the Ets-1 proto-oncogene in human gastric carcinoma: correlation with tumor invasion. The American journal of pathology 101 8952528
2004 The Ets-1 transcription factor is involved in the development and invasion of malignant melanoma. Cellular and molecular life sciences : CMLS 100 14704859
2008 Mechanical strain induces osteogenic differentiation: Cbfa1 and Ets-1 expression in stretched rat mesenchymal stem cells. International journal of oral and maxillofacial surgery 92 18272346
2020 MicroRNA-221/222 Mediates ADSC-Exosome-Induced Cardioprotection Against Ischemia/Reperfusion by Targeting PUMA and ETS-1. Frontiers in cell and developmental biology 84 33344446
2010 Transcription factor Ets-1 in cytokine and chemokine gene regulation. Cytokine 84 20378371
2007 Ets-1 regulates plasma cell differentiation by interfering with the activity of the transcription factor Blimp-1. The Journal of biological chemistry 84 17977828
2004 The structural and dynamic basis of Ets-1 DNA binding autoinhibition. The Journal of biological chemistry 84 15591056
2003 Ets-1 and Ets-2 transcription factors are essential for normal coronary and myocardial development in chicken embryos. Circulation research 77 12637368
2000 Involvement of the Ets-1 gene in overexpression of matrilysin in human hepatocellular carcinoma. Cancer research 76 11103822
2012 MicroRNA-146a and Ets-1 gene polymorphisms in ocular Behcet's disease and Vogt-Koyanagi-Harada syndrome. Annals of the rheumatic diseases 75 23268366
2001 Expression of the ets-1 proto-oncogene in human colorectal carcinoma. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 74 11353051
2018 ETS-1 induces Sorafenib-resistance in hepatocellular carcinoma cells via regulating transcription factor activity of PXR. Pharmacological research 73 30114438
2006 Ets-1 and runx2 regulate transcription of a metastatic gene, osteopontin, in murine colorectal cancer cells. The Journal of biological chemistry 71 16670084
1998 Ets-1 is an early response gene activated by ET-1 and PDGF-BB in vascular smooth muscle cells. The American journal of physiology 71 9486138
2012 Ets-1 is a transcriptional mediator of oncogenic nitric oxide signaling in estrogen receptor-negative breast cancer. Breast cancer research : BCR 70 22971289
2011 Ets-1 mediates upregulation of Mcl-1 downstream of XBP-1 in human melanoma cells upon ER stress. Oncogene 63 21423203
2002 Sp100 interacts with ETS-1 and stimulates its transcriptional activity. Molecular and cellular biology 61 11909962
2017 Usp9x regulates Ets-1 ubiquitination and stability to control NRAS expression and tumorigenicity in melanoma. Nature communications 57 28198367
2005 Ets-1 expression promotes epithelial cell transformation by inducing migration, invasion and anchorage-independent growth. Oncogene 57 15940256
2004 Ets-1 regulates TNF-alpha-induced matrix metalloproteinase-9 and tenascin expression in primary bronchial fibroblasts. Journal of immunology (Baltimore, Md. : 1950) 57 14734780
2003 EAPII interacts with ETS1 and modulates its transcriptional function. Oncogene 57 12743594
2005 Overexpression of Ets-1 proto-oncogene in latent and clinical prostatic carcinomas. Histopathology 56 15693893
2008 The affinity of Ets-1 for DNA is modulated by phosphorylation through transient interactions of an unstructured region. Journal of molecular biology 52 18692067
1999 Ets-1 positively regulates expression of urokinase-type plasminogen activator (uPA) and invasiveness of astrocytic tumors. Journal of neuropathology and experimental neurology 52 10218628
2011 Altered levels of Ets-1 transcription factor and matrix metalloproteinases in melanocytes from patients with vitiligo. The British journal of dermatology 51 21428970
1992 Serum, AP-1 and Ets-1 stimulate the human ets-1 promoter. Nucleic acids research 51 1614856
2008 Regulation of the transcription factor Ets-1 by DNA-mediated homo-dimerization. The EMBO journal 50 18566588
2004 Transcription factor Ets-1 mediates ischemia- and vascular endothelial growth factor-dependent retinal neovascularization. The American journal of pathology 50 15111329
2006 Regulation of the Ets-1 transcription factor by sumoylation and ubiquitinylation. Oncogene 49 16862185
2005 Overexpression of Ets-1 in human hematopoietic progenitor cells blocks erythroid and promotes megakaryocytic differentiation. Cell death and differentiation 49 16294212
2010 Ets-1 regulates energy metabolism in cancer cells. PloS one 47 21042593
2003 Ets-1 expression is associated with cranial neural crest migration and vasculogenesis in the chick embryo. Gene expression patterns : GEP 47 12915311
2019 Breast cancer invasion and progression by MMP-9 through Ets-1 transcription factor. Gene 46 31265880
2013 Ets-1 facilitates nuclear entry of NFAT proteins and their recruitment to the IL-2 promoter. Proceedings of the National Academy of Sciences of the United States of America 46 24019486
2010 Ets-1 maintains IL-7 receptor expression in peripheral T cells. Journal of immunology (Baltimore, Md. : 1950) 46 21148801
2001 Role of transcription factors in angiogenesis: Ets-1 promotes angiogenesis as well as endothelial apoptosis. Annals of the New York Academy of Sciences 46 11795259
2013 Ets-1 regulates intracellular glutathione levels: key target for resistant ovarian cancer. Molecular cancer 45 24238102
2012 ETS transcription factors and prostate cancer: the role of the family prototype ETS-1 (review). International journal of oncology 45 22366814
1991 Structural and functional analysis of the regulatory sequences of the ets-1 gene. Oncogene 45 1945412
1999 Expression of the Ets-1 proto-oncogene correlates with malignant potential in human astrocytic tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 44 10392639
2014 MicroRNA-124 inhibits cellular proliferation and invasion by targeting Ets-1 in breast cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 43 25085587
2003 Expression of an Ets-1 dominant-negative mutant perturbs normal and tumor angiogenesis in a mouse ear model. Oncogene 42 12660815
2016 miR-144-3p, a tumor suppressive microRNA targeting ETS-1 in laryngeal squamous cell carcinoma. Oncotarget 40 26826553
2008 Ets-1 upregulates HER2-induced MMP-1 expression in breast cancer cells. Biochemical and biophysical research communications 40 18851945
2006 Properties and regulation of a transiently assembled ERK2.Ets-1 signaling complex. Biochemistry 40 17105191
2018 Ets-1 promoter-associated noncoding RNA regulates the NONO/ERG/Ets-1 axis to drive gastric cancer progression. Oncogene 39 29773901
2012 Interaction of Ets-1 with HDAC1 represses IL-10 expression in Th1 cells. Journal of immunology (Baltimore, Md. : 1950) 39 22266280
2000 Expression and possible role of ets-1 in hepatocellular carcinoma. American journal of clinical pathology 39 11068545
2000 Association with Ets-1 causes ligand- and AF2-independent activation of nuclear receptors. Molecular and cellular biology 39 11073980
2005 The transcription factor Ets-1 in breast cancer. Frontiers in bioscience : a journal and virtual library 38 15574387
2002 Ets-1 upregulates matrix metalloproteinase-1 expression through extracellular matrix adhesion in vascular endothelial cells. Biochemical and biophysical research communications 37 11829472
2000 Renal expression of the Ets-1 proto-oncogene during progression of rat crescentic glomerulonephritis. Journal of the American Society of Nephrology : JASN 37 11095647
2018 Ets-1 drives breast cancer cell angiogenic potential and interactions between breast cancer and endothelial cells. International journal of oncology 36 30365153
2008 The transcription factor ETS-1: its role in tumour development and strategies for its inhibition. Mini reviews in medicinal chemistry 36 18855726
2008 Essential contribution of Ets-1 to constitutive Pim-3 expression in human pancreatic cancer cells. Cancer science 36 19154409
1995 ets-1 in astrocytes: expression and transmitter-evoked phosphorylation. Molecular and cellular biology 35 7823957
2016 Negative Correlation Between miR-326 and Ets-1 in Regulatory T Cells from new-Onset SLE Patients. Inflammation 34 26861134
2010 Ets-1 expression and gemcitabine chemoresistance in pancreatic cancer cells. Cellular & molecular biology letters 34 21225469
2008 Ets-1 triggers and orchestrates the malignant phenotype of mammary cancer cells within their matrix environment. Journal of cellular physiology 34 18181172
2004 Expression and function of Ets-1 during experimental acute renal failure in rats. Journal of the American Society of Nephrology : JASN 33 15579511
2019 Endothelial-specific deletion of Ets-1 attenuates Angiotensin II-induced cardiac fibrosis via suppression of endothelial-to-mesenchymal transition. BMB reports 32 30670148
2015 TLR9-induced miR-155 and Ets-1 decrease expression of CD1d on B cells in SLE. European journal of immunology 32 25929465
2011 Expression of Ets-1, Ang-2 and maspin in ovarian cancer and their role in tumor angiogenesis. Journal of experimental & clinical cancer research : CR 32 21439064
2015 Lupus Risk Variant Increases pSTAT1 Binding and Decreases ETS1 Expression. American journal of human genetics 31 25865496
2002 Ets-1 and integrin beta3 for lung metastasis from colorectal cancer. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 31 12076271
2019 Ets-1 deficiency alleviates nonalcoholic steatohepatitis via weakening TGF-β1 signaling-mediated hepatocyte apoptosis. Cell death & disease 30 31189885
2014 MicroRNA-146a and Ets-1 gene polymorphisms are associated with pediatric uveitis. PloS one 30 24658012
2012 ETS1 regulates the expression of ATXN2. Human molecular genetics 30 22914732
2004 STAT6 and Ets-1 form a stable complex that modulates Socs-1 expression by interleukin-4 in keratinocytes. The Journal of biological chemistry 30 15199062
2002 Expression of ets-1 and ets-2 in colonic neoplasms. Anticancer research 30 12168840
2021 EHF suppresses cancer progression by inhibiting ETS1-mediated ZEB expression. Oncogenesis 29 33712555
2016 MicroRNA221-3p modulates Ets-1 expression in synovial fibroblasts from patients with osteoarthritis of temporomandibular joint. Osteoarthritis and cartilage 29 27349463
2014 Ets-1 controls breast cancer cell balance between invasion and growth. International journal of cancer 29 24706481
2011 The dual nature of Ets-1: focus to the pathogenesis of systemic lupus erythematosus. Autoimmunity reviews 29 21296190
2006 PIASy-mediated repression of the Ets-1 is independent of its sumoylation. Biochemical and biophysical research communications 29 16729975
2022 ETS-1 facilitates Th1 cell-mediated mucosal inflammation in inflammatory bowel diseases through upregulating CIRBP. Journal of autoimmunity 28 35926374
2008 Ets-1 mediates platelet-derived growth factor-BB-induced thrombomodulin expression in human vascular smooth muscle cells. Cardiovascular research 28 19091791
2006 Transcription factor Ets-1 is essential for mesangial matrix remodeling. Kidney international 28 16738537
2022 GATA4 Regulates Developing Endocardium Through Interaction With ETS1. Circulation research 27 36263775

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