Affinage

ELK3

ETS domain-containing protein Elk-3 · UniProt P41970

Length
407 aa
Mass
44.2 kDa
Annotated
2026-06-09
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ELK3 (Net/SAP-2/ERP) is an ETS-domain ternary complex factor that interacts with serum response factor at the c-fos serum response element and controls gene programs governing angiogenesis, EMT, and development (PMID:7540136, PMID:31018569). Its DNA-binding and transcriptional output are autoregulated by a C-terminal negative regulatory domain (the Net Inhibitory Domain, an HLH-like ~50-residue region) whose repression is relieved by Ras-ERK signaling and by phosphorylation of conserved S/T-P motifs in the activation domain by ERK2 and by RSK2, the latter binding ELK3 directly and driving its nuclear accumulation (PMID:7909357, PMID:8918463, PMID:7540136, PMID:31018569). ELK3 functions context-dependently as a repressor or activator: it represses NOS2, HO-1 (via the EBS1 site), and CXCL16, and antagonizes ETS-1 at the MT1-MMP promoter to restrain VEGF-induced angiogenesis, while it activates HIF-1α/VEGF-A signaling, ECM-remodeling genes, and angiogenic programs in other settings (PMID:12896968, PMID:16456000, PMID:36950218, PMID:24719561, PMID:37452291). In development and tissue homeostasis it is required for neural crest cell progression upstream of FoxD3/Sox10/Snail2, for retinal vascular patterning through Angiopoietin/Tie signaling, for endothelial barrier integrity downstream of the ALDH2-LIN28B mRNA-stability axis, and for ILC3 differentiation when its promoter is opened by the circTmem241-Nono-Ash1l complex (PMID:23266330, PMID:25203538, PMID:37822152, PMID:35953472). In cancer, ELK3 promotes invasion, EMT, and metastasis through the ELK3-GATA3 and ZEB1/E-cadherin axes and shapes chemosensitivity and NK-cell-mediated immunity by controlling mitochondrial dynamics via Mid51 and DRP1/DNM1L (PMID:27556500, PMID:31511359, PMID:35858708, PMID:37422450). ELK3 protein levels are set by opposing ubiquitin machinery: SPOP-mediated, checkpoint-kinase-assisted ubiquitination drives its degradation, whereas UCHL5 deubiquitinates and stabilizes it (PMID:38632244, PMID:36328194).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1994 High

    Established the domain logic of ELK3 by showing that the full-length protein binds DNA poorly until its C-terminus is removed, defining an intrinsic negative regulatory domain.

    Evidence PCR cloning with gel-shift and deletion-mutant analysis on ETS sites

    PMID:7909357

    Open questions at the time
    • Did not define how the C-terminal block is relieved physiologically
    • No partner proteins identified
  2. 1995 High

    Placed ELK3 in the TCF/SRF axis and connected its activity to growth-factor signaling, showing it forms ternary complexes at the c-fos SRE and is phosphorylated by ERK2.

    Evidence In vitro ternary complex/binding assays, transfection, and in vitro ERK2 kinase assay

    PMID:7540136

    Open questions at the time
    • In vivo ternary complex was weak and serum-insensitive
    • Functional consequence of activation-domain phosphorylation not resolved
  3. 1995 High

    Distinguished ELK3 from paralogs ELK1 and ELK4 by mapping it to a separate chromosomal locus.

    Evidence In situ hybridization on banded mouse and human chromosomes

    PMID:8575773

    Open questions at the time
    • No functional information added
  4. 1996 High

    Defined the structural basis of autoinhibition, identifying the Net Inhibitory Domain as an HLH-like module that blocks DNA binding and is overcome by Ras, and linked ELK3 to bHLH factor E47.

    Evidence Reporter assays, NID residue mutagenesis, heterologous fusions, and co-IP with E47

    PMID:8918463

    Open questions at the time
    • No experimental structure of the NID
    • Functional role of E47 interaction not established
  5. 2003 High

    Demonstrated ELK3 as a bona fide transcriptional repressor of an endogenous target, showing NOS2 repression requires both the NID and ETS domains.

    Evidence Promoter assays, NID/ETS mutagenesis, Northern blot, and mouse endotoxemia model

    PMID:12896968

    Open questions at the time
    • Direct promoter occupancy at NOS2 not shown by ChIP
    • Did not address how LPS down-regulates ELK3
  6. 2006 High

    Extended the repressor role to HO-1 with site resolution, showing ELK3 acts specifically through the EBS1 element and that its LPS-driven loss permits HO-1 induction.

    Evidence Promoter assays with EBS1/EBS2 mutagenesis, qRT-PCR, and mouse lung tissue

    PMID:16456000

    Open questions at the time
    • Mechanism of ELK3 down-regulation by LPS still unknown at this stage
  7. 2008 Medium

    Provided a pharmacological handle on the Ras-ERK-Net axis and unexpectedly tied Net signaling to microtubule dynamics via the inhibitor XRP44X.

    Evidence Cell-based reporter screen, phosphorylation assays, and tubulin colchicine-site binding

    PMID:18316589

    Open questions at the time
    • Single lab
    • Whether microtubule effects feed back on ELK3 in vivo unresolved
  8. 2012 High

    Defined a developmental requirement, placing ELK3 in the neural crest gene regulatory network downstream of neural plate border genes and upstream of NC specifiers.

    Evidence Loss-of-function knockdown in avian embryos with in situ hybridization and marker analysis

    PMID:23266330

    Open questions at the time
    • Direct ELK3 targets in this network not identified
    • Avian model only
  9. 2014 High

    Established ELK3's vascular and angiogenic functions through complementary loss-of-function studies and identified direct promoter targets (MT1-MMP, MIR155HG) and a regulatory miRNA loop.

    Evidence Elk3 KO mice, aortic ring/tube assays, Matrigel plug, ChIP/ChIP-seq, and 3'-UTR validation

    PMID:24719561 PMID:25203538 PMID:25401928

    Open questions at the time
    • Whether retinal Ang/Tie phenotype is cell-autonomous to ELK3 targets unresolved
    • Direction of ELK3 (repressor vs activator) varies by context
  10. 2014 High

    Resolved how ELK3 itself is transcriptionally controlled in macrophages, identifying KLF4/Sp1 competition at a GC-rich promoter element and linking ELK3 to phagocytosis via HO-1.

    Evidence Promoter assays, ChIP for KLF4/Sp1, mutagenesis, and phagocytosis assays in HO-1 KO macrophages

    PMID:25351511

    Open questions at the time
    • Upstream signals controlling KLF4/Sp1 switch not fully defined
  11. 2016 High

    Defined ELK3 as a metastasis-promoting factor in TNBC acting through epigenetic silencing of GATA3, and linked it to HIF-1α in liver cancer stem cells and to autophagy via PI3K/Akt.

    Evidence shRNA knockdown, expression profiling, double-knockdown rescue, invasion/migration and autophagy assays

    PMID:27301639 PMID:27556500 PMID:27959451

    Open questions at the time
    • Mechanism of GATA3 epigenetic regulation by ELK3 not fully defined
    • HIF-1α and autophagy links are Medium-confidence
  12. 2017 Medium

    Connected ELK3 to fibrotic EMT via Egr-1 under p38 MAPK and to lymphangiogenesis via NF-κB-driven VEGF-C.

    Evidence siRNA knockdown, EMT/Egr-1 Westerns, p38 inhibition, CCl4 fibrosis and xenograft models

    PMID:27538444 PMID:28188790

    Open questions at the time
    • Direct ELK3 binding to Egr-1 or VEGFC loci not shown
    • Single lab
  13. 2019 High

    Mapped direct ELK3 kinase and EMT-cofactor interactions, showing RSK2 binds and phosphorylates ELK3 to drive nuclear localization and c-fos/AP-1 activity, and ZEB1 both activates ELK3 transcription and physically partners with it to repress E-cadherin.

    Evidence Reciprocal Co-IP and GST pull-down with domain mapping, phosphorylation and reporter assays, and exosomal miRNA functional assays

    PMID:31018569 PMID:31182803 PMID:31511359

    Open questions at the time
    • Structural basis of RSK2-ELK3 and ZEB1-ELK3 contacts unresolved
    • Exosomal miRNA findings are Medium-confidence single-lab
  14. 2020 High

    Identified additional downstream effectors of ELK3 in cancer, including miR-200a as a direct repressor of ELK3 and an AKT-SERPINE1 axis controlling prostate cancer cell behavior.

    Evidence 3'-UTR reporter and rescue assays, extravasation model, cell-cycle/apoptosis assays, and AKT inhibitor treatment

    PMID:32104682 PMID:32414208

    Open questions at the time
    • SERPINE1 regulation may be indirect
    • AKT-SERPINE1 link is Medium-confidence
  15. 2022 High

    Defined how ELK3 protein abundance is set by deubiquitination and how chromatin opening initiates its transcription, while linking ELK3 to mitochondrial fission and immune evasion.

    Evidence UCHL5 deubiquitination assays, circTmem241-Nono-Ash1l ChIP/ATAC-seq with KO rescue, and Mid51/mitochondrial dynamics with NK cytotoxicity assays

    PMID:35858708 PMID:35953472 PMID:36328194

    Open questions at the time
    • UCHL5 and Mid51 findings are Medium-confidence single-lab
    • How ELK3 transcriptionally controls Mid51 not shown by direct occupancy
  16. 2023 High

    Consolidated ELK3 control points and outputs, defining ALDH2-LIN28B mRNA-stability control of ELK3 in endothelial barrier function, HIF-1α/VEGF-A-driven glioma angiogenesis, CXCL16 repression shaping NK immunity, and DRP1/DNM1L-mediated chemosensitivity.

    Evidence Co-IP for ALDH2-LIN28B, endothelial-specific KO mice and AAA model, angiogenesis assays, NK cytotoxicity, and cisplatin/mitochondrial fission assays

    PMID:36950218 PMID:37422450 PMID:37452291 PMID:37822152

    Open questions at the time
    • Cancer angiogenesis/immunity links largely Medium-confidence single-lab
    • Direct ELK3 occupancy at CXCL16 and DNM1L not uniformly demonstrated
  17. 2024 High

    Completed the proteostasis picture by identifying SPOP as the E3 ligase that, aided by checkpoint-kinase phosphorylation, degrades ELK3 to restrain c-Fos-driven proliferation and influence docetaxel response.

    Evidence Co-IP, ubiquitination and phosphorylation assays, SPOP knockdown/mutation, and IHC of 123 prostate cancer specimens

    PMID:38632244

    Open questions at the time
    • Identity of the specific checkpoint kinase phosphosites not fully resolved
    • Interplay between SPOP and UCHL5 on the same substrate not directly tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ELK3's repressor-versus-activator choice is determined at individual target genes, and how its many upstream regulators (kinases, ubiquitin machinery, miRNAs, mRNA-stability factors) are integrated in a given cell, remains unresolved.
  • No unified model for context-dependent repression vs activation
  • No genome-wide direct target map integrated across tissues
  • No experimental structure of full-length ELK3 or its regulatory domains

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3
Partners
E47ERK2ETS1RSK2SPOPSRFUCHL5ZEB1
Complex memberships
ternary complex factor (TCF)-SRF complex at c-fos SRE

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 ERP/SAP-2 (ELK3) is a ternary complex factor (TCF) that interacts with Serum Response Factor (SRF) and the c-fos Serum Response Element (SRE) through conserved regions; however, in vitro ternary complex formation by SAP-2 is strongly inhibited by its C-terminal sequences, and ternary complex formation in vivo is weak and largely unaffected by serum stimulation or v-ras co-expression. The C-terminal transcriptional activation domain of ELK3 is phosphorylated following growth factor stimulation at conserved S/T-P motifs, and the activation domain can be phosphorylated in vitro by partially purified ERK2. In vitro transcription/binding assays, transient transfection, in vitro kinase assay with ERK2 The EMBO journal High 7540136
1994 ELK3 (ERP) encodes an ETS-domain transcription factor; full-length ERP shows negligible DNA-binding activity by itself, but removal of the carboxy-terminal domain enables binding to ets-binding sites (E74 site, IgH enhancer pi site, lck promoter ets site), demonstrating that the C-terminus functions as a negative regulatory domain inhibiting DNA binding. PCR cloning, gel-shift/EMSA, deletion mutant analysis Molecular and cellular biology High 7909357
1996 Net (ELK3/ERP/SAP-2) represses transcription under basal conditions through its Net Inhibitory Domain (NID), a ~50 amino acid region that autoregulates Net and inhibits when fused to heterologous proteins. The NID adopts a helix-loop-helix (HLH)-like structure, inhibits DNA binding, and can be overcome by Ras activation through the C-domain. Net interacts in vivo with the basic HLH factor E47. Transient transfection reporter assays, deletion/mutagenesis of NID residues, co-immunoprecipitation (in vivo interaction with E47), structure prediction and model building The EMBO journal High 8918463
2003 Elk-3 (Net/Erp/Sap-2a) markedly represses NOS2 (inducible nitric-oxide synthase 2) promoter activity in macrophages in a dose-dependent fashion, requiring both the Net Inhibitory Domain and the ETS DNA-binding domain; overexpression of Elk-3 blunts induction of endogenous NOS2 mRNA. Endogenous Elk-3 mRNA is down-regulated by LPS before NOS2 induction, and TGF-β1 increases Elk-3 levels while inversely correlating with NOS2 down-regulation. Transient transfection promoter assays, mutagenesis of Elk-3 NID and ETS domains, Northern blot for endogenous mRNA, in vivo mouse endotoxemia model The Journal of biological chemistry High 12896968
2006 Endotoxin-induced down-regulation of Elk-3 facilitates heme oxygenase-1 (HO-1) induction in macrophages. Elk-3 represses HO-1 promoter activity specifically through the EBS1 Ets binding site (at bp -125 of the murine HO-1 promoter), distinct from the EBS2 site used by activating factors. LPS decreases Elk-3 mRNA levels preceding HO-1 up-regulation both in macrophages and in mouse lung tissue. Transient transfection promoter assays, site-directed mutagenesis of EBS1/EBS2, quantitative RT-PCR, in vivo mouse endotoxemia model Journal of immunology High 16456000
2008 Net (Elk-3/SAP-2/Erp) is phosphorylated and activated by Ras-ERK signaling. A novel pyrazole, XRP44X, inhibits FGF-2-induced Net phosphorylation by the Ras-Erk pathway upstream of Ras. XRP44X also binds to the colchicine-binding site of tubulin and depolymerizes microtubules, connecting microtubule-targeting activity to inhibition of the Ras-Net pathway. Cell-based reporter screen for Ras activation of Net, phosphorylation assays, tubulin binding assay, cytoskeletal morphology analysis Cancer research Medium 18316589
2012 Elk3 is essential for neural crest cell progression from progenitor to definitive neural crest cell in the avian embryo. Loss of Elk3 results in retention of Pax7+ precursors in the dorsal neural tube that fail to upregulate neural crest specifier genes FoxD3, Sox10, and Snail2, causing severe migration defects. Epistasis places Elk3 downstream of neural plate border genes but upstream of neural crest specifier genes in the NC gene regulatory network. Whole mount in situ hybridization, quantitative RT-PCR, loss-of-function knockdown in avian embryos, immunofluorescence for marker genes Developmental biology High 23266330
2014 Elk3 deficiency in mice causes transient delay of post-natal retinal angiogenesis and formation of tortuous arteries in adults. Elk3 knockout results in altered expression of Angiopoietin/Tie-signalling components, reduced in vitro microvessel sprouting and microtube formation from aortic ring explants. No changes in VEGF or mural cell coverage were observed, implicating Ang/Tie signaling as the mechanism. Elk3 knockout mouse generation, retinal flat-mount analysis, aortic ring sprouting assay, gene expression analysis PloS one High 25203538
2014 ELK3 suppresses VEGF-induced angiogenesis in endothelial cells by inhibiting ETS-1 transcriptional activity on the MT1-MMP promoter. ELK3 knockdown reinforces tube formation in HUVECs and increases angiogenesis in vivo (Matrigel plug assay). ChIP assay confirmed ELK3 binding to the MT1-MMP promoter, and MT1-MMP knockdown in ELK3-knockdown cells decreases tube formation, placing MT1-MMP downstream of ELK3. siRNA knockdown, HUVEC tube formation assay, Matrigel plug in vivo assay, luciferase reporter assay, ChIP assay International journal of biological sciences High 24719561
2014 Elk-3 expression in macrophages is down-regulated by LPS through increased binding of the transcriptional repressor KLF4 to a GC-rich region (bp -613 to -603) of the Elk-3 promoter, while Sp1 binding to the same region is decreased. Overexpression of Elk-3 in the presence of E. coli bacteria results in decreased macrophage phagocytosis, an effect phenocopied by HO-1 deficiency. Promoter activity assays, GC-rich region mutagenesis, ChIP assay for KLF4 and Sp1 binding, bacterial phagocytosis assay, bone marrow-derived macrophages from HO-1 KO mice Journal of leukocyte biology High 25351511
2014 ELK3 and hsa-miR-155-5p form a double-negative regulatory loop: ELK3 depletion induces hsa-miR-155-5p expression, and hsa-miR-155-5p decreases ELK3 expression via a conserved target sequence in its 3'-UTR. ELK3 chromatin binding at the MIR155HG transcription start site was confirmed by ChIP-seq and ChIP-qPCR in HUVECs. Both factors affect in vitro angiogenesis and wound closure similarly. ChIP-seq, ChIP-qPCR, miRNA expression analysis, 3'-UTR target validation, in vitro angiogenesis and wound closure assays PloS one High 25401928
2016 Suppression of ELK3 in MDA-MB-231 triple-negative breast cancer cells leads to transdifferentiation from an invasive mesenchymal phenotype to a non-invasive epithelial phenotype, with epigenetic activation of GATA3 (a master suppressor of metastasis). Suppression of GATA3 in ELK3-knockdown cells restores invasion and migration, establishing the ELK3-GATA3 axis as a major pathway controlling metastasis. shRNA knockdown, gene expression profiling, rescue experiments (double knockdown), in vitro and in vivo invasion/migration assays Oncotarget High 27556500
2016 ELK3 promotes migration and invasion of CD133+/CD44+ liver cancer stem cells (LCSCs) by modulating HIF-1α expression; silencing ELK3 in LCSCs attenuates metastatic potential and reduces HIF-1α levels. siRNA knockdown, migration and invasion assays, Western blotting for HIF-1α Oncology reports Medium 27959451
2016 Suppression of ELK3 in MDA-MB-231 breast cancer cells impairs autophagy under starvation conditions and causes hypersensitivity to doxorubicin. The mechanism involves activation of the PI3K/Akt pathway as the primary cause of impaired autophagy in ELK3 knockdown cells. siRNA knockdown, autophagy assays, PI3K/Akt pathway analysis, doxorubicin sensitivity assay Biochemical and biophysical research communications Medium 27301639
2017 Elk-3 contributes to the progression of liver fibrosis by modulating epithelial-mesenchymal transition (EMT) via regulation of Egr-1 under MAPK signaling. Elk-3 expression is regulated by p38 MAPK phosphorylation during TGF-β1-induced EMT, and silencing Elk-3 suppresses EMT marker expression. siRNA knockdown, Western blotting for EMT markers and Egr-1, p38 MAPK inhibition, in vivo CCl4 liver fibrosis model Gut and liver Medium 27538444
2017 ELK3 regulates peritumoral lymphangiogenesis and VEGF-C production in triple-negative breast cancer cells. Suppression of ELK3 reduces VEGFC expression through suppression of NF-κB signaling, implicating ELK3 as an upstream regulator of the NF-κB pathway controlling lymphatic vessel development. shRNA knockdown, VEGF-C measurement, NF-κB pathway analysis, in vitro lymphatic endothelial cell assays, in vivo xenograft model Biochemical and biophysical research communications Medium 28188790
2019 RSK2 directly interacts with ELK3 through RSK2's N-terminal kinase and linker domains and ELK3's D and C domains, leading to phosphorylation of ELK3, enhanced c-fos promoter activity, and AP-1 transactivation. RSK2 deficiency reduces ELK3 nuclear localization. This RSK2-ELK3 signaling axis promotes cancer cell proliferation and colony growth. Co-immunoprecipitation, domain deletion mapping, phosphorylation assay, reporter assay, immunocytofluorescence for nuclear localization, RSK2 knockdown/knockout International journal of molecular sciences High 31018569
2019 ZEB1 functions as a transcriptional activator of ELK3 expression, and ZEB1 and ELK3 directly bind each other (demonstrated by GST pull-down and co-immunoprecipitation with domain deletion mutants). ZEB1 and ELK3 collaborate to repress E-cadherin expression, establishing ELK3 as a novel factor in the ZEB1/E-cadherin EMT axis. GST pull-down assay, co-immunoprecipitation with domain deletion mutants, promoter activity assay for ELK3 by ZEB1, E-cadherin reporter assay Molecular cancer research High 31511359
2019 ELK3 expressed in lymphatic endothelial cells (LECs) promotes breast cancer cell migration and invasion via exosomal miRNAs (miR-503-3p, miR-4269, miR-30e-3p). Suppression of ELK3 in LECs diminishes pro-oncogenic exosome activity, and ELK3 is identified as a master regulator of the tumor microenvironment-tumor communication axis in breast cancer. shRNA knockdown, conditioned medium assays, exosome isolation and functional assays, miRNA expression profiling, in vivo xenograft model Scientific reports Medium 31182803
2020 miR-200a directly targets the 3' UTR of ELK3 mRNA to destabilize transcripts, thereby impairing migration and invasion of TNBC cells. In vivo, miR-200a transfection reduced extravasation of MDA-MB-231 cells into the lung, and co-transfection with ELK3 lacking an intact 3'-UTR rescued extravasation ability, confirming ELK3 as a direct functional target of miR-200a. 3'-UTR luciferase reporter assay, miRNA mimic transfection, in vitro migration/invasion assays, in vivo tail vein injection extravasation model, rescue by 3'-UTR-deleted ELK3 construct Cancers High 32414208
2020 Silencing ELK3 in DU145 prostate cancer cells induces S-M phase arrest, promotes apoptosis, and inhibits migration; the migration inhibition is partly mediated by upregulation of SERPINE1 via activation of the AKT pathway. AKT inhibitor treatment attenuates SERPINE1 expression induced by ELK3 knockdown, establishing the AKT-SERPINE1 axis as a downstream pathway of ELK3. siRNA knockdown, cell cycle analysis, apoptosis assay, migration assay, Western blotting, xenograft model, AKT inhibitor treatment BioMed research international Medium 32104682
2021 ELK3 modulates ECM remodeling in gastric cancer cells to facilitate migration and invasion, regulating genes including BMP1, LOXL2, SNAI1, SERPINF1, DCN, and NID1. In silico and in vitro analyses confirmed positive association between ELK3 expression and these ECM remodeling-related genes. siRNA knockdown, migration/invasion assays, gene expression analysis (qPCR/Western blot), in silico correlation analysis in patient data International journal of molecular sciences Medium 35409069
2022 UCHL5 deubiquitinase directly deubiquitinates and stabilizes ELK3 protein in pancreatic adenocarcinoma cells, promoting cancer stemness and tumor progression. ELK3 downstream effects involve activation of Notch1 signaling. UCHL5 deficiency suppresses stemness features, which are rescued by ectopic ELK3 expression. Co-immunoprecipitation, ubiquitination assay, UCHL5 overexpression/knockdown, ELK3 rescue experiments, RNA-seq pathway analysis Experimental cell research Medium 36328194
2022 ELK3-dependent mitochondrial fission-fusion status is linked to mitochondrial superoxide concentration in TNBC cells and determines NK cell-mediated immune responses. Mid51 (a mediator of mitochondrial fission) was identified as a direct downstream target of ELK3, with ELK3 expression inversely correlating with Mid51. shRNA/plasmid modulation of ELK3, mitochondrial dynamics analysis, ROS measurement, NK cell cytotoxicity assay, gene expression profiling, in vivo xenograft model Journal for immunotherapy of cancer Medium 35858708
2022 CircTmem241 interacts with Nono protein to recruit histone methyltransferase Ash1l onto the Elk3 promoter in ILC progenitor cells (ILCPs), inducing histone modifications that enhance chromatin accessibility and initiate Elk3 transcription, which drives ILC3 differentiation. Overexpression of Elk3 rescues impaired ILC3 differentiation in circTmem241-/-, Nono-/-, and Ash1l-/- cells. CircRNA-protein interaction assays, ChIP for Ash1l and histone marks at Elk3 promoter, ATAC-seq for chromatin accessibility, ILC3 differentiation assays, genetic rescue with Elk3 overexpression, knockout mice Nature communications High 35953472
2023 ALDH2 directly binds to LIN28B, a regulator of ELK3 mRNA stability, hindering LIN28B binding to ELK3 mRNA and thereby depressing ELK3 expression, which impairs endothelial barrier function. ELK3 acts as a downstream regulator of ALDH2 for endothelial barrier function preservation in abdominal aortic aneurysm. ALDH2 knockdown/knockout in endothelial cells increases EC barrier markers and suppresses early aortic dilation. Single-cell RNA-seq, mRNA sequencing, Co-IP (ALDH2-LIN28B binding), ALDH2 endothelial-specific KD/KO mouse models, barrier integrity assays, in vivo AAA model Advanced science High 37822152
2023 ELK3 promotes glioma angiogenesis by activating the HIF-1α/VEGF-A signaling axis; silencing ELK3 inhibits VEGF-A expression and secretion by facilitating HIF-1α degradation via ubiquitination. siRNA knockdown, ELISA for VEGF-A, Western blot for HIF-1α ubiquitination, tube formation assay, aortic ring sprouting, Matrigel plug assay, orthotopic xenograft in nude mice BMC cancer Medium 37452291
2023 ELK3 depletion in TNBC cells increases CXCL16 expression and promotes NK cell cytotoxicity through CXCL16-mediated NK cell recruitment; ELK3 negatively regulates CXCL16, suggesting ELK3 acts as a transcriptional repressor of CXCL16. shRNA knockdown, CXCL16 expression analysis, NK cell recruitment assay, NK cell cytotoxicity assay, in silico correlation analysis Oncoimmunology Medium 36950218
2023 ELK3 determines chemosensitivity of TNBC cells to cisplatin (CDDP) by regulating mitochondrial dynamics. DNM1L (encoding DRP1, a major regulator of mitochondrial fission) is identified as a direct downstream target of ELK3, with ELK3 knockdown rendering cells more susceptible to CDDP through accelerated mitochondrial fission, ROS production, and DNA damage. shRNA knockdown, cisplatin sensitivity assay, mitochondrial fission analysis, ROS measurement, DNA damage assay, ChIP or promoter analysis for DNM1L Cell death discovery Medium 37422450
2024 SPOP E3 ubiquitin ligase directly interacts with ELK3 and promotes its ubiquitination and proteasomal degradation, assisted by checkpoint kinase-mediated phosphorylation of ELK3. SPOP-mediated ELK3 destabilization suppresses c-Fos-induced cell proliferation and invasion in prostate cancer. SPOP-depleted or mutated prostate cancer cells show resistance to docetaxel-induced cell death, correlating with elevated ELK3 protein levels. Co-immunoprecipitation (SPOP-ELK3 interaction), ubiquitination assay, checkpoint kinase phosphorylation assay, SPOP knockdown/mutation, proliferation and invasion assays, immunohistochemistry of 123 PCa tissues Cell death & disease High 38632244
1995 The chromosomal locations of ELK3 (Net/SAP-2) were mapped to mouse chromosome 10C-D1 and human chromosome 12q22-q23, establishing it as a distinct gene product from ELK1 and ELK4 with different chromosomal localizations in both mouse and human genomes. In situ hybridization on banded chromosomes with specific cDNA probes Genomics High 8575773

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Three stages of facial expression processing: ERP study with rapid serial visual presentation. NeuroImage 396 19770052
1995 Comparative analysis of the ternary complex factors Elk-1, SAP-1a and SAP-2 (ERP/NET). The EMBO journal 258 7540136
2003 Complement resistance of Borrelia burgdorferi correlates with the expression of BbCRASP-1, a novel linear plasmid-encoded surface protein that interacts with human factor H and FHL-1 and is unrelated to Erp proteins. The Journal of biological chemistry 183 14607842
1996 Disruption of the erp/mkp-1 gene does not affect mouse development: normal MAP kinase activity in ERP/MKP-1-deficient fibroblasts. Oncogene 181 8806681
1993 Structure, mapping, and expression of erp, a growth factor-inducible gene encoding a nontransmembrane protein tyrosine phosphatase, and effect of ERP on cell growth. Molecular and cellular biology 180 8355678
2011 Rett syndrome mutation MeCP2 T158A disrupts DNA binding, protein stability and ERP responses. Nature neuroscience 167 22119903
1994 ERP, a new member of the ets transcription factor/oncoprotein family: cloning, characterization, and differential expression during B-lymphocyte development. Molecular and cellular biology 119 7909357
1977 Estrogen receptor protein (ERP) in multiple tumor specimens from individual patients with breast cancer. Cancer 96 870169
2002 Linkage and linkage disequilibrium mapping of ERP and EEG phenotypes. Biological psychology 81 12385677
1996 Net (ERP/SAP2) one of the Ras-inducible TCFs, has a novel inhibitory domain with resemblance to the helix-loop-helix motif. The EMBO journal 79 8918463
2018 Visual Mismatch and Predictive Coding: A Computational Single-Trial ERP Study. The Journal of neuroscience : the official journal of the Society for Neuroscience 76 29581379
2006 Mycobacterium marinum Erp is a virulence determinant required for cell wall integrity and intracellular survival. Infection and immunity 76 16714540
2004 Immunological characterization of the complement regulator factor H-binding CRASP and Erp proteins of Borrelia burgdorferi. International journal of medical microbiology : IJMM 76 15146998
1995 An ERP study on the specificity of facial expression processing. International journal of psychophysiology : official journal of the International Organization of Psychophysiology 71 7558985
2004 Molecular characterization of Borrelia burgdorferi erp promoter/operator elements. Journal of bacteriology 67 15090516
2008 Inhibition of the Ras-Net (Elk-3) pathway by a novel pyrazole that affects microtubules. Cancer research 65 18316589
2012 Changes in bacterial growth rate govern expression of the Borrelia burgdorferi OspC and Erp infection-associated surface proteins. Journal of bacteriology 56 23222718
2016 ELK3 promotes the migration and invasion of liver cancer stem cells by targeting HIF-1α. Oncology reports 50 27959451
2014 An optimized ERP brain-computer interface based on facial expression changes. Journal of neural engineering 49 24743165
2019 ELK3 expressed in lymphatic endothelial cells promotes breast cancer progression and metastasis through exosomal miRNAs. Scientific reports 47 31182803
2017 Tumor-suppressive miRNA-135a inhibits breast cancer cell proliferation by targeting ELK1 and ELK3 oncogenes. Genes & genomics 46 29892795
2014 Following the time course of face gender and expression processing: a task-dependent ERP study. International journal of psychophysiology : official journal of the International Organization of Psychophysiology 46 24594443
2008 Lyme borreliosis spirochete Erp proteins, their known host ligands, and potential roles in mammalian infection. International journal of medical microbiology : IJMM 46 18248770
2016 PI3K/Akt/mTOR activation by suppression of ELK3 mediates chemosensitivity of MDA-MB-231 cells to doxorubicin by inhibiting autophagy. Biochemical and biophysical research communications 43 27301639
2013 Fearful, surprised, happy, and angry facial expressions modulate gaze-oriented attention: behavioral and ERP evidence. Social neuroscience 43 24047232
2006 Borrelia burgdorferi EbfC, a novel, chromosomally encoded protein, binds specific DNA sequences adjacent to erp loci on the spirochete's resident cp32 prophages. Journal of bacteriology 41 16740939
2013 Single-trial ERP analysis reveals facial expression category in a three-stage scheme. Brain research 39 23566819
2012 Race, emotion and trust: an ERP study. Brain research 39 23220554
2019 Long Non-Coding RNA LINC00525 Promotes the Stemness and Chemoresistance of Colorectal Cancer by Targeting miR-507/ELK3 Axis. International journal of stem cells 38 31242722
2014 The oncogenic MicroRNA Hsa-miR-155-5p targets the transcription factor ELK3 and links it to the hypoxia response. PloS one 38 25401928
2022 ELK3 Controls Gastric Cancer Cell Migration and Invasion by Regulating ECM Remodeling-Related Genes. International journal of molecular sciences 36 35409069
2020 LINC01106 post-transcriptionally regulates ELK3 and HOXD8 to promote bladder cancer progression. Cell death & disease 35 33311496
2003 Elk-3 is a transcriptional repressor of nitric-oxide synthase 2. The Journal of biological chemistry 35 12896968
2002 Simultaneous coexpression of Borrelia burgdorferi Erp proteins occurs through a specific, erp locus-directed regulatory mechanism. Journal of bacteriology 35 12142424
1995 Characterization of the Mycobacterium tuberculosis erp gene encoding a potential cell surface protein with repetitive structures. Microbiology (Reading, England) 35 7496523
2001 Erp, an extracellular protein family specific to mycobacteria. Microbiology (Reading, England) 34 11496008
2011 BpaB and EbfC DNA-binding proteins regulate production of the Lyme disease spirochete's infection-associated Erp surface proteins. Journal of bacteriology 33 22155777
2006 Borrelia burgdorferi erp genes are expressed at different levels within tissues of chronically infected mammalian hosts. International journal of medical microbiology : IJMM 33 16530008
2021 Face and emotional expression processing under continuous perceptual load tasks: An ERP study. Biological psychology 32 33636248
2019 RSK2-Mediated ELK3 Activation Enhances Cell Transformation and Breast Cancer Cell Growth by Regulation of c-fos Promoter Activity. International journal of molecular sciences 32 31018569
2016 The ELK3-GATA3 axis orchestrates invasion and metastasis of breast cancer cells in vitro and in vivo. Oncotarget 32 27556500
2014 Face the hierarchy: ERP and oscillatory brain responses in social rank processing. PloS one 32 24622288
1998 Interleukins and their antagonists but not TNF and its receptors are released in post-ERP pancreatitis. European journal of gastroenterology & hepatology 32 9855088
2014 Elk-3 is a KLF4-regulated gene that modulates the phagocytosis of bacteria by macrophages. Journal of leukocyte biology 31 25351511
2005 Expression of Borrelia burgdorferi erp genes during infection of non-human primates. Microbial pathogenesis 31 15964737
2010 BpaB, a novel protein encoded by the Lyme disease spirochete's cp32 prophages, binds to erp Operator 2 DNA. Nucleic acids research 30 20421207
2008 Evidence for modulation of facial emotional processing bias during emotional expression decoding by serotonergic and noradrenergic antidepressants: an event-related potential (ERP) study. Psychopharmacology 30 18825371
2020 ERP evidence for emotional sensitivity in social anxiety. Journal of affective disorders 29 33099050
2019 ZEB1 Collaborates with ELK3 to Repress E-Cadherin Expression in Triple-Negative Breast Cancer Cells. Molecular cancer research : MCR 29 31511359
2014 Comprehending body language and mimics: an ERP and neuroimaging study on Italian actors and viewers. PloS one 28 24608244
2014 ELK3 suppresses angiogenesis by inhibiting the transcriptional activity of ETS-1 on MT1-MMP. International journal of biological sciences 28 24719561
2006 Endotoxin-induced down-regulation of Elk-3 facilitates heme oxygenase-1 induction in macrophages. Journal of immunology (Baltimore, Md. : 1950) 26 16456000
2021 Methyltransferase-like protein 11A promotes migration of cervical cancer cells via up-regulating ELK3. Pharmacological research 25 34450313
1999 ERP effects of spatial attention and display search with unilateral and bilateral stimulus displays. Biological psychology 25 10461806
2020 Silencing of ELK3 Induces S-M Phase Arrest and Apoptosis and Upregulates SERPINE1 Expression Reducing Migration in Prostate Cancer Cells. BioMed research international 24 32104682
2018 LemA and Erp Y-like recombinant proteins from Leptospira interrogans protect hamsters from challenge using AddaVax™ as adjuvant. Vaccine 24 29625765
2018 Implicit Emotion Regulation Deficits in Trait Anxiety: An ERP Study. Frontiers in human neuroscience 23 30323748
2015 Fearful contextual expression impairs the encoding and recognition of target faces: an ERP study. Frontiers in behavioral neuroscience 23 26388751
2014 Hyper-attenuated MTBVAC erp mutant protects against tuberculosis in mice. Vaccine 23 25066740
1993 Expression of the nontransmembrane tyrosine phosphatase gene erp during mouse organogenesis. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 23 8274454
2023 Early Progression of Abdominal Aortic Aneurysm is Decelerated by Improved Endothelial Barrier Function via ALDH2-LIN28B-ELK3 Signaling. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 22 37822152
2020 Functional Link between miR-200a and ELK3 Regulates the Metastatic Nature of Breast Cancer. Cancers 22 32414208
2021 Emotion, Gender and Gaze Discrimination Tasks do not Differentially Impact the Neural Processing of Angry or Happy Facial Expressions-a Mass Univariate ERP Analysis. Brain topography 21 34596796
2017 Elk-3 Contributes to the Progression of Liver Fibrosis by Regulating the Epithelial-Mesenchymal Transition. Gut and liver 21 27538444
2012 Elk3 is essential for the progression from progenitor to definitive neural crest cell. Developmental biology 21 23266330
2009 Identification of two proteins that interact with the Erp virulence factor from Mycobacterium tuberculosis by using the bacterial two-hybrid system. BMC molecular biology 21 19159459
2004 The Erp protein is anchored at the surface by a carboxy-terminal hydrophobic domain and is important for cell-wall structure in Mycobacterium smegmatis. FEMS microbiology letters 21 14987764
1995 Locations of the ets subfamily members net, elk1, and sap1 (ELK3, ELK1, and ELK4) on three homologous regions of the mouse and human genomes. Genomics 21 8575773
2022 Circular RNA circTmem241 drives group III innate lymphoid cell differentiation via initiation of Elk3 transcription. Nature communications 20 35953472
2022 Deubiquitinase UCHL5 stabilizes ELK3 to potentiate cancer stemness and tumor progression in pancreatic adenocarcinoma (PAAD). Experimental cell research 20 36328194
2021 The Effects of Dynamic and Static Emotional Facial Expressions of Humans and Their Avatars on the EEG: An ERP and ERD/ERS Study. Frontiers in neuroscience 20 33967681
2020 Implicit emotion regulation deficits in individuals with high schizotypal traits: an ERP study. Scientific reports 20 32127580
2020 LINC00662 promotes cell proliferation, migration and invasion of melanoma by sponging miR-890 to upregulate ELK3. European review for medical and pharmacological sciences 20 32894549
2018 ELK3-GATA3 axis modulates MDA-MB-231 metastasis by regulating cell-cell adhesion-related genes. Biochemical and biophysical research communications 20 29510139
2015 ELK3 Expression Correlates With Cell Migration, Invasion, and Membrane Type 1-Matrix Metalloproteinase Expression in MDA-MB-231 Breast Cancer Cells. Gene expression 20 26637400
2003 The allele encoding the mycobacterial Erp protein affects lung disease in mice. Cellular microbiology 20 12542471
2022 ELK3 modulates the antitumor efficacy of natural killer cells against triple negative breast cancer by regulating mitochondrial dynamics. Journal for immunotherapy of cancer 19 35858708
2021 Arithmetic performance is modulated by cognitive reappraisal and expression suppression: Evidence from behavioral and ERP findings. Neuropsychologia 18 34653496
2018 Background Odors Modulate N170 ERP Component and Perception of Emotional Facial Stimuli. Frontiers in psychology 18 29997539
2016 XRP44X, an Inhibitor of Ras/Erk Activation of the Transcription Factor Elk3, Inhibits Tumour Growth and Metastasis in Mice. PloS one 17 27427904
2011 Foveal and parafoveal spatial attention and its impact on the processing of facial expression: an ERP study. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology 17 21889396
2019 Contextual effects of angry vocal expressions on the encoding and recognition of emotional faces: An event-related potential (ERP) study. Neuropsychologia 16 31325481
2017 The role of ELK3 to regulate peritumoral lymphangiogenesis and VEGF-C production in triple negative breast cancer cells. Biochemical and biophysical research communications 16 28188790
2014 Elk3 deficiency causes transient impairment in post-natal retinal vascular development and formation of tortuous arteries in adult murine retinae. PloS one 15 25203538
2009 Switching associations between facial identity and emotional expression: a behavioural and ERP study. NeuroImage 15 19962443
2016 ERP comparison study of face gender and expression processing in unattended condition. Neuroscience letters 14 26930625
2015 Crystal structures of the Erp protein family members ErpP and ErpC from Borrelia burgdorferi reveal the reason for different affinities for complement regulator factor H. Biochimica et biophysica acta 14 25582082
2023 Facemasks selectively impair the recognition of facial expressions that stimulate empathy: An ERP study. Psychophysiology 13 36847283
2023 Glioma angiogenesis is boosted by ELK3 activating the HIF-1 /VEGF-A signaling axis. BMC cancer 13 37452291
2020 PIM1 inhibition attenuated endotoxin-induced acute lung injury through modulating ELK3/ICAM1 axis on pulmonary microvascular endothelial cells. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 13 33185705
2020 Emotional reactivity and regulation in 5- to 8-year-old children: An ERP study of own-age face processing. International journal of psychophysiology : official journal of the International Organization of Psychophysiology 12 32711016
2018 Reward association alters brain responses to emotional stimuli: ERP evidence. International journal of psychophysiology : official journal of the International Organization of Psychophysiology 12 30423356
2017 Associations between the oxytocin receptor gene (OXTR) rs53576 polymorphism and emotional processing of social and nonsocial cues: an event-related potential (ERP) study. Journal of physiological anthropology 12 28126018
2023 The ELK3-DRP1 axis determines the chemosensitivity of triple-negative breast cancer cells to CDDP by regulating mitochondrial dynamics. Cell death discovery 11 37422450
2015 Emotional conflict in facial expression processing during scene viewing: an ERP study. Brain research 11 25747865
2023 ELK3-CXCL16 axis determines natural killer cell cytotoxicity via the chemotactic activity of CXCL16 in triple negative breast cancer. Oncoimmunology 10 36950218
2021 ELK3 Mediated by ZEB1 Facilitates the Growth and Metastasis of Pancreatic Carcinoma by Activating the Wnt/β-Catenin Pathway. Frontiers in cell and developmental biology 10 34409034
2012 Mismatched expressions decrease face recognition and corresponding ERP old/new effects in schizophrenia. Neuropsychology 10 22686352
2011 Age differences on ERP old/new effects for emotional and neutral faces. International journal of psychophysiology : official journal of the International Organization of Psychophysiology 10 22138004
2024 ELK3 destabilization by speckle-type POZ protein suppresses prostate cancer progression and docetaxel resistance. Cell death & disease 9 38632244

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