Affinage

ELK1

ETS domain-containing protein Elk-1 · UniProt P19419

Length
428 aa
Mass
44.9 kDa
Annotated
2026-06-09
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ELK1 is an ETS-domain transcription factor that converts MAP kinase signalling into immediate-early and context-specific transcriptional programmes (PMID:1630903, PMID:7651411, PMID:22589737). Its amino-terminal ETS domain (residues 1-93) is an independently folded mixed α/β module that binds DNA with high affinity and specificity without bending it, while flanking sequences including a B-box protein-protein interaction domain mediate ternary complex formation with SRF on serum response elements (PMID:1630903, PMID:7890710, PMID:9010223). ELK1 is a direct substrate of ERK and stress-activated JNK/SAPK kinases, with which it physically associates; phosphorylation—notably at Ser383—activates its transcriptional output and drives target genes such as c-fos (PMID:8339245, PMID:8208531, PMID:7651411, PMID:32034306). This activation is opposed by calcineurin (PP2B), which specifically dephosphorylates Ser383 to provide negative cross-talk between Ca2+ and MAPK signalling, and full transcriptional activation additionally requires nuclear Ca2+ downstream of phosphorylation (PMID:10329725, PMID:11971908). ELK1 activity is further gated by SUMO conjugation at lysines 230/249/254, which promotes nuclear retention and dampens output; ERK activation employs a two-step mechanism that strips SUMO while adding activating phosphorylation (PMID:15210726, PMID:16626293). Through two distinct DNA-binding modes—an SRF-dependent ternary mode and a unique mode at sites not bound by other ETS factors—ELK1 controls separable gene classes, including genes governing cell migration (PMID:22589737). Beyond classical immediate-early activation, ELK1 acts as a direct transcriptional repressor at promoters such as ITGB6 and smooth-muscle genes, and as an activator at promoters including GDH1, BCL6, MLCK, miR-17-92 and BACH2/BACH1, cooperating with chromatin regulators p300, CHD8 and SETD8 to execute context-specific programmes across endothelial, immune, neuronal, fibrotic and cancer settings (PMID:16260603, PMID:24121020, PMID:26861876, PMID:26472816, PMID:32034306, PMID:36575212, PMID:29129929, PMID:34953958, PMID:35351142, PMID:36377663). In neurons it functions downstream of an ERK/DJ-1 axis to drive antioxidant and survival responses (PMID:21796667, PMID:36261683).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1992 High

    Established the modular architecture underlying ELK1 DNA recognition, defining which domains read DNA directly versus those needed to partner with SRF.

    Evidence Domain deletion and point mutagenesis with DNA-binding and ternary complex assays

    PMID:1630903

    Open questions at the time
    • Did not resolve how phosphorylation alters these binding modes
    • No structural model of the ternary complex
  2. 1995 High

    Defined the ETS domain as an autonomous high-affinity DNA-binding fold that engages DNA without inducing bending, anchoring the recognition mechanism structurally.

    Evidence NMR/CD/fluorescence spectroscopy and circular-permutation bending analysis on purified ETS domain

    PMID:7890710

    Open questions at the time
    • Structure of full-length protein not determined
    • Did not address SRF-bound conformation
  3. 1995 High

    Placed ELK1 as a convergent substrate of both ERK and stress-activated JNK/SAPK pathways, explaining how distinct stimuli feed the same factor.

    Evidence In vitro kinase assays with purified SAPK/ERK and Elk-1, plus cell-based phosphorylation and c-fos readouts

    PMID:7651411 PMID:8208531 PMID:8339245

    Open questions at the time
    • Relative contribution of each kinase in vivo unresolved
    • Full set of phosphoacceptor sites not enumerated here
  4. 1997 High

    Identified upstream signalling architecture (cAMP/Rap1/B-Raf) feeding ELK1 activation and showed it links to neuronal differentiation, establishing cell-type-specific routing into ELK1.

    Evidence PC12 transfection with dominant-negative/activated mutants and Elk-1 reporter assays

    PMID:9094716

    Open questions at the time
    • Did not identify direct ELK1 target genes for differentiation
    • Mechanism of B-Raf vs Raf-1 selectivity on ELK1 output unaddressed
  5. 1999 High

    Showed ELK1 activity is reversibly controlled at a single critical residue, with calcineurin dephosphorylating Ser383 to integrate Ca2+ with MAPK input.

    Evidence Constitutively active calcineurin cotransfection, Ca2+ ionophore, phospho-Ser383 Western and c-fos reporter; brain-slice glutamate/ERK studies

    PMID:10329725 PMID:9858538

    Open questions at the time
    • Other phosphosites' regulation by phosphatases not mapped
    • Specificity of calcineurin for ELK1 in vivo incompletely defined
  6. 2002 High

    Revealed that ELK1 phosphorylation is necessary but not sufficient, with nuclear Ca2+ required downstream for full transactivation, and that menin can uncouple ERK activity from ELK1 phosphorylation.

    Evidence Compartment-targeted parvalbumin with GAL4-Elk-1 reporter; menin overexpression with kinase and reporter assays

    PMID:11971908 PMID:12226747

    Open questions at the time
    • Nuclear Ca2+ effector acting on ELK1 not identified
    • Mechanism by which menin blocks phosphorylation unresolved
  7. 2006 High

    Defined SUMOylation as a second, antagonistic layer of control, with ERK simultaneously removing SUMO and adding activating phosphorylation in a two-step activation switch.

    Evidence In vitro/in vivo SUMOylation assays, triple-lysine mutant, heterokaryon export and PC12 neurite assays; PIASx-alpha co-activator model

    PMID:15210726 PMID:16626293

    Open questions at the time
    • Symposium synthesis (idx 12) builds on primary data
    • Deconjugating enzyme and kinetics of SUMO removal not defined
  8. 2012 High

    Genome-wide mapping resolved that ELK1 uses two binding modes—redundant ETS sites and unique sites—to control separable gene programmes including cell migration.

    Evidence ChIP-seq with loss-of-function, migration assays and expression profiling

    PMID:22589737

    Open questions at the time
    • Determinants directing ELK1 to unique vs redundant sites unknown
    • Cofactor differences between the two modes not defined
  9. 2018 High

    Showed ELK1 functions as a direct repressor as well as activator across tissues—repressing BACH2 in B cells, ITGB6 in fibrosis, and smooth-muscle genes—broadening its role beyond immediate-early activation.

    Evidence ChIP/ChIP-seq, reporter mutagenesis, knockdown and Elk1-knockout mouse models with disease phenotypes

    PMID:16260603 PMID:26861876 PMID:29129929 PMID:30068599

    Open questions at the time
    • Switch between activator and repressor functions mechanistically unexplained
    • Corepressor identity at repressed promoters not defined
  10. 2022 High

    Established ELK1 as a recruiter of chromatin machinery, showing it is required to bring CHD8, p300 and SETD8/H4K20me1 to specific promoters to execute context-specific transcription.

    Evidence ATAC-seq, ChIP, Co-IP, GST pulldown and RNA-IP in neurons, cholangiocytes and EndMT models

    PMID:34953958 PMID:35351142 PMID:36575212

    Open questions at the time
    • Direct vs indirect nature of some chromatin-factor interactions not fully resolved
    • Whether recruitment depends on ELK1 phosphorylation state untested
  11. 2022 High

    Placed ELK1 as a transcriptional effector of oncogenic and metabolic programmes (GDH1 glutaminolysis, BCL6 downstream of mutant KRAS) and of neuroprotection/regeneration via an ERK/DJ-1/SOD1 axis.

    Evidence ChIP, Ser383 point mutation, metabolic assays, KRAS-mutant and optic-nerve-crush in vivo models; DJ-1 Co-IP and knockout

    PMID:21796667 PMID:32034306 PMID:36261683 PMID:36377663

    Open questions at the time
    • Selectivity of these target promoters across cell types unexplained
    • How upstream pathway choice dictates ELK1 target repertoire unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what molecular determinants dictate whether ELK1 activates or represses a given promoter and which cofactor it engages, i.e. how a single MAPK-driven factor is routed into divergent context-specific programmes.
  • No unifying model linking phosphorylation/SUMO state to activator vs repressor outcome
  • Cofactor selection rules undefined
  • No structure of ELK1 in complex with chromatin regulators

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 3 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 4
Partners
CHD8ERK2P300PARP1PIAS1SAP1ASETD8SRF
Complex memberships
ELK1-SRF ternary complex

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 The amino-terminal ETS domain of Elk-1 is necessary and sufficient for direct DNA binding, while both the ETS domain and flanking sequences up to amino acid 169 (including a protein-protein interaction domain spanning residues 137-169) are required for ternary complex formation with the c-fos SRE and SRF. A single amino acid exchange in the ETS domain can alter direct DNA-binding affinity without severely affecting SRF-assisted binding. Domain deletion analysis and mutagenesis with DNA-binding and ternary complex formation assays Nucleic acids research High 1630903
1993 Elk-1 proteins are phosphoproteins that act as substrates and activators of MAP kinases (ERK/p44mpk); purified Elk-1 stimulates MAP kinase autophosphorylation and activation in an ATP/Mg2+-dependent manner. Dephosphorylation studies indicate Elk-1 can activate only tyrosine-phosphorylated MAP kinase. In vitro kinase assays with purified recombinant proteins; co-immunoprecipitation; dephosphorylation experiments Cancer research Medium 8339245
1994 Elk-1 proteins physically interact with MAP kinases (ERK1/ERK2); co-immunoprecipitation confirmed specific association. In vitro phosphorylation of Elk-1 by MAP kinase was not regulatory for autonomous DNA-binding activity of Elk-1. Co-immunoprecipitation with purified recombinant proteins; in vitro phosphorylation assays; EGF-stimulated cell lysate kinase assays with GST-Elk-1 Oncogene Medium 8208531
1995 The ETS DNA-binding domain of Elk-1 (residues 1-93) is an independently folded domain of mixed alpha/beta structure; it binds DNA with high affinity (Kd ~0.85×10^-10 M) and specificity without inducing significant DNA bending. Protein overexpression and purification; CD, NMR, and fluorescence spectroscopy; circular permutation DNA-bending analysis; quantitative DNA-binding assays The Journal of biological chemistry High 7890710
1995 Both the MAPK (ERK) and stress-activated protein kinase (SAPK/JNK) pathways converge on Elk-1; purified p54 SAPK-alpha efficiently phosphorylates the Elk-1 C-terminal domain in vitro. Prolonged SAPK activation correlates with sustained Elk-1 phosphorylation and c-fos transcription. In vitro kinase assay with purified p54 SAPK-alpha; in-gel kinase assays; Western blotting for Elk-1 phosphorylation Molecular and cellular biology High 7651411
1997 cAMP activates Elk-1 and induces neuronal differentiation of PC12 cells via a B-Raf- and Rap1-dependent pathway upstream of MAP kinase. Rap1 activated by PKA selectively activates B-Raf but inhibits Raf-1, conferring cell-type specificity. PC12 cell transfection; dominant-negative and activated mutant expression; Elk-1 reporter assays; MAP kinase activity assays Cell High 9094716
1997 ELK1 and SAP1a form ternary complexes with SRF on the Egr1 promoter serum response elements (SREI and SREII), and ELK1 and SAP1a also form quaternary complexes on Egr1 SREI. The B-box domain of ELK1 is required for SRF interaction. Gel mobility shift assays; deletion mutant analysis; in vitro transcription/translation Oncogene Medium 9010223
1999 Calcineurin (protein phosphatase 2B) specifically dephosphorylates Elk-1 at phosphoserine 383, a critical site whose phosphorylation by MAPK promotes transcriptional activity, thereby providing negative cross-talk between Ca2+ signaling and MAPK-mediated Elk-1 activation. Cotransfection with constitutively active calcineurin; Ca2+ ionophore treatment; Western blotting for phospho-Ser383 Elk-1; c-fos reporter assays The Journal of biological chemistry High 10329725
1999 In rat striatal brain slices, glutamate stimulates ERK-dependent phosphorylation of Elk-1 at Ser383 and c-fos induction; this is blocked by the MEK inhibitor PD98059. CaM-K activity positively regulates ERK activation upstream of Elk-1. Brain slice preparation; pharmacological inhibitors (PD98059, KN62); phospho-specific Western blotting; c-fos mRNA detection Molecular and cellular biology Medium 9858538
2002 EGF-mediated transcriptional activation of Elk-1 requires nuclear calcium. Suppression of nuclear (but not cytosolic) Ca2+ signals by targeted parvalbumin expression inhibits EGF-induced Elk-1 transactivation without affecting ERK phosphorylation, its nuclear translocation, or Elk-1 phosphorylation—indicating that nuclear Ca2+ is required downstream of Elk-1 phosphorylation for full transcriptional activation. Targeted parvalbumin expression (nuclear vs. cytosolic); GAL4-Elk-1 reporter assay; ERK phosphorylation and nuclear translocation assays The Journal of biological chemistry High 11971908
2002 Menin (encoded by MEN1) inhibits ERK-dependent phosphorylation and activation of Elk-1 without interfering with ERK2 activation itself, acting downstream of MAPK. Menin also inhibits JNK-mediated phosphorylation of c-Jun/JunD through a distinct inhibitory mechanism. Menin overexpression; in vitro kinase assays for ERK2 and JNK1 activity; Western blotting for Elk-1 phosphorylation; Elk-1 and c-fos reporter assays; N-terminal deletion mutants Oncogene Medium 12226747
2004 Elk-1 is conjugated to SUMO at lysines 230, 249, and/or 254; mutation of all three sites (Elk-1-3R) is required to fully block SUMOylation in vitro and in vivo. SUMO conjugation promotes nuclear retention of Elk-1, and loss of SUMOylation (Elk-1-3R) enhances cytoplasmic shuttling and augments neurite extension in PC12 cells. In vitro and in vivo SUMOylation assays; heterokaryon nuclear export assays; PC12 neurite extension; SUMO-1/-2 overexpression; mutant Ubc9 coexpression The Journal of cell biology High 15210726
2006 ERK pathway activation leads to SUMO loss from Elk-1 simultaneously as ERK promotes Elk-1 phosphorylation/activation, employing a two-step mechanism to fully activate Elk-1. PIASx-alpha acts as a co-activator facilitating this process. Biochemical analysis of SUMO modification changes upon ERK activation; reporter assays; PIASx-alpha coexpression Biochemical Society symposium Medium 16626293
2005 Elk-1 inhibits smooth muscle-specific gene expression (telokin, SM22alpha) by blocking myocardin-induced promoter activation and by binding to a nonconsensus site in the telokin promoter in an SRF-dependent manner. Differential sensitivity of smooth muscle promoters to Elk-1 depends on both the DNA-binding domain and the SRF-binding B-box. Overexpression and dominant-negative Elk-1 in SMCs; gel mobility shift assays; chromatin immunoprecipitation; promoter reporter assays; site-directed mutagenesis Molecular and cellular biology High 16260603
2007 Phosphorylated ERK2 directly interacts with PARP-1 and activates it in a DNA-independent manner in a cell-free system; activated PARP-1 in turn dramatically increases ERK2-catalyzed phosphorylation of Elk-1. This PARP-1/ERK2/Elk-1 axis enhances c-fos transcription and histone acetylation in neurons. Cell-free reconstitution with recombinant PARP-1 and phospho-ERK2; ERK2 kinase assay for Elk-1 phosphorylation; cortical neuron and cardiomyocyte experiments with PARP inhibitors Molecular cell High 17244536
2012 ChIP-seq reveals ELK1 uses two distinct DNA binding modes: one where other ETS factors can bind redundantly, and another unique mode binding sites not occupied by other ETS factors. The unique binding mode controls a distinct subset of genes, including those governing cell migration. ChIP-seq; loss-of-function experiments; cell migration assays; gene expression profiling PLoS genetics High 22589737
2013 TNF-α activates ERK1/2, which phosphorylates and activates Elk-1; activated Elk-1 translocates to the nucleus and binds its motif on the MLCK promoter, activating MLCK transcription and increasing intestinal tight junction permeability. ERK1/2 pathway inhibitors; Elk-1 siRNA; MLCK promoter reporter assay; ChIP for Elk-1 binding; in vivo intestinal perfusion model The American journal of pathology Medium 24121020
2011 DJ-1 interacts with Erk1/2 and is required for nuclear translocation of Erk1/2 upon oxidative stimulation; nuclear Erk1/2 activates Elk1, which promotes SOD1 (Cu/Zn-superoxide dismutase-1) expression as a neuroprotective response. Co-immunoprecipitation of DJ-1 with Erk1/2; DJ-1 knockdown cells and knockout mice; Elk1 activation assays; SOD1 expression measurement Annals of neurology Medium 21796667
2016 Reduced Elk-1 expression causes enhanced ITGB6 (beta6 integrin subunit) expression; Elk-1 basally binds the ITGB6 promoter and represses it. Loss of Elk-1 in vivo exaggerates lung fibrosis, identifying Elk-1 as a transcriptional repressor of integrin αvβ6. ChIP for Elk-1 at ITGB6 promoter; ITGB6 promoter reporter assays; Elk-1 knockdown; Elk1 knockout mouse model of lung fibrosis The Journal of biological chemistry High 26861876
2015 VEGF activates Erk/Elk1 in endothelial cells, leading to Elk-1-mediated transcriptional activation of the miR-17-92 cluster; ChIP confirmed Elk-1 occupancy at the miR-17-92 promoter. This upregulation is required for EC proliferation and angiogenic sprouting. ChIP assay for Elk-1 at miR-17-92 promoter; VEGF stimulation with ERK/ELK1 inhibition; miR-17-92 iEC-KO mice for in vivo angiogenesis Circulation research High 26472816
2019 EGFR activates MEK/ERK signaling, which phosphorylates ELK1 at Ser383; phosphorylated ELK1 binds the GDH1 promoter to activate its transcription, thereby promoting glutamine metabolism in glioblastoma. ELK1 knockdown or Ser383 mutation abolishes EGFR-driven glutaminolysis. ELK1 knockdown; Ser383 point mutation; ChIP for ELK1 at GDH1 promoter; MEK/ERK inhibitors; metabolic assays Oncogene High 32034306
2019 PIAS1 is phosphorylated by MAPK/ERK at a novel site Ser503, which determines its E3 ligase activity; PIAS1 then SUMOylates Elk-1 in rat brain, which decreases Elk-1 phosphorylation and downregulates GADD45α expression. Elk-1-SUMO1 reduces hippocampal apoptosis in APP/PS1 Alzheimer's disease model mice. LC-MS/MS phosphoproteomics; in vitro kinase assay; in vitro SUMOylation assay; lentiviral Elk-1-SUMO1 expression; TUNEL assay in APP/PS1 mice British journal of pharmacology High 30849179
2022 ELK1 is necessary to recruit CHD8 specifically to ETS motif-containing promoters in human neurons; loss of ELK1 prevents CHD8 from binding these sites. ELK1 and CHD8 functionally cooperate to regulate gene expression at MAPK/ERK target genes. Conditional loss-of-function and endogenous tagging of CHD8 in iPSC-derived neurons; chromatin accessibility (ATAC-seq); transcriptional profiling; ELK1 knockdown with ChIP for CHD8 Scientific reports High 36575212
2022 In retinal ganglion cells, Elk-1 is both necessary and sufficient for neuroprotection and axon regeneration after optic nerve injury; its activity is enhanced by specific phosphorylation site manipulation. Epistasis experiments show Elk-1 acts downstream of PTEN and is inhibited by REST in the survival/regeneration pathway. In vivo AAV-mediated Elk-1 overexpression and phosphomutant expression; optic nerve crush model; dominant-negative experiments; genetic epistasis with PTEN and REST Scientific reports Medium 36261683
2018 ERK/ELK1 signaling directs plasma cell differentiation by repressing BACH2; ELK1 controls an active regulatory region within the BACH2 super-enhancer. RNA-seq and ChIP-seq confirmed ELK1-dependent BACH2 repression in IL-2-stimulated human naive B cells. ChIP-seq for ELK1 at BACH2 super-enhancer; RNA-seq; IL-2 stimulation with ERK pathway inhibitors; BACH2 overexpression rescue Nature communications High 29129929
2018 ELK-1 overexpression in mouse hippocampus produces depressive-like behaviors; selective inhibition of ELK-1 activation prevents stress-induced depression-like molecular and behavioral states. ELK-1 mRNA is upregulated in postmortem hippocampus from depressed suicides. Hippocampal ELK-1 viral overexpression; stress models in mice; ELK-1 selective inhibition; behavioral assays; molecular/synaptic plasticity readouts Nature medicine Medium 29736027
2021 The lncRNA ACTA2-AS1 facilitates recruitment of the p300/ELK1 complex to the PDGFB promoter after LPS exposure in cholangiocytes; this drives p300-mediated H3K27 acetylation and transcriptional activation of proliferative/fibrogenic genes. The complex was confirmed by co-immunoprecipitation, RNA-IP, and ChIP. Co-immunoprecipitation of p300 and ELK1; RNA-IP; ChIP for p300/ELK1 occupancy and H3K27ac at PDGFB promoter; ACTA2-AS1 depletion organoids Journal of hepatology Medium 34953958
2022 SETD8 directly interacts with ELK1 (Co-IP and GST pulldown); ELK1 binds the bach1 promoter to activate its transcription; H4K20me1 (downstream of SETD8) co-occupies the bach1 promoter with ELK1. Mutual inhibition between SETD8 and ELK1 regulates EndMT in diabetic nephropathy. Co-immunoprecipitation; GST pulldown; ChIP for ELK1 and H4K20me1 at bach1 promoter; dual-luciferase assay with ELK1 binding site deletion Journal of translational medicine Medium 35351142
2018 ERK signaling through ELK4 (SAP-1) and ELK1 in the thymus cell-autonomously suppresses innate-like αβ CD8+ T cell differentiation; mice lacking both ELK4 and ELK1 develop increased innate-like CD8+ T cells. The effect is mediated via ELK4/ELK1-SRF target genes including EGR2. ELK4 and ELK1 double-knockout mice; T cell development analysis; EGR2 overexpression rescue; ERK pathway inhibition in peripheral CD8+ T cells Journal of immunology Medium 30068599
2019 Elk-1 transcription factor is identified as a candidate regulator of prodromal transcriptional changes in Huntington's disease (HD); AAV-mediated Elk-1 overexpression in R6/1 mice alleviated transcriptional dysregulation. Exogenous Elk-1 expression exerted beneficial effects in primary striatal HD cell culture. Transcriptional and chromatin profiling (H3K27ac) in R6/1 mice; AAV-Elk-1 overexpression in vivo; primary striatal HD cell culture Proceedings of the National Academy of Sciences Medium 31744868
2022 ELK1 directly binds the BCL6 promoter and activates its transcription as part of the MAPK/ERK/ELK1 axis downstream of mutant KRAS; ChIP and reporter assays confirmed ELK1 occupancy and transcriptional regulation of BCL6. ChIP for ELK1 at BCL6 promoter; luciferase reporter assay; MEK/ERK inhibitors; ELK1 knockdown; KRAS-mutant lung cancer mouse model (LSL-KrasG12D/+) The Journal of clinical investigation High 36377663
2010 ELK1 directly binds to the FADS2 promoter in an allele-specific manner at SNP rs968567; this binding was demonstrated by electrophoretic mobility shift assay, showing the minor allele abolishes ELK1 binding and reduces FADS2 promoter activity. Electrophoretic mobility shift assay (EMSA); luciferase reporter gene assays; supershift with anti-ELK1 antibody Journal of lipid research Medium 19546342

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 cAMP activates MAP kinase and Elk-1 through a B-Raf- and Rap1-dependent pathway. Cell 938 9094716
2007 DNA-independent PARP-1 activation by phosphorylated ERK2 increases Elk1 activity: a link to histone acetylation. Molecular cell 285 17244536
1999 Glutamate induces phosphorylation of Elk-1 and CREB, along with c-fos activation, via an extracellular signal-regulated kinase-dependent pathway in brain slices. Molecular and cellular biology 276 9858538
1998 Growth hormone stimulates phosphorylation and activation of elk-1 and expression of c-fos, egr-1, and junB through activation of extracellular signal-regulated kinases 1 and 2. The Journal of biological chemistry 232 9813041
1995 Protein synthesis inhibitors reveal differential regulation of mitogen-activated protein kinase and stress-activated protein kinase pathways that converge on Elk-1. Molecular and cellular biology 231 7651411
2013 TNF-α modulation of intestinal epithelial tight junction barrier is regulated by ERK1/2 activation of Elk-1. The American journal of pathology 211 24121020
2000 TNF receptor family member BCMA (B cell maturation) associates with TNF receptor-associated factor (TRAF) 1, TRAF2, and TRAF3 and activates NF-kappa B, elk-1, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase. Journal of immunology (Baltimore, Md. : 1950) 210 10903733
2018 Nrf2/ARE pathway attenuates oxidative and apoptotic response in human osteoarthritis chondrocytes by activating ERK1/2/ELK1-P70S6K-P90RSK signaling axis. Free radical biology & medicine 139 29339024
2015 VEGF-Induced Expression of miR-17-92 Cluster in Endothelial Cells Is Mediated by ERK/ELK1 Activation and Regulates Angiogenesis. Circulation research 134 26472816
1992 Elk-1 protein domains required for direct and SRF-assisted DNA-binding. Nucleic acids research 131 1630903
2019 Circular RNA hsa_circ_0000515 acts as a miR-326 sponge to promote cervical cancer progression through up-regulation of ELK1. Aging 122 31772143
1997 FLI1 and EWS-FLI1 function as ternary complex factors and ELK1 and SAP1a function as ternary and quaternary complex factors on the Egr1 promoter serum response elements. Oncogene 98 9010223
2017 IL-2 imprints human naive B cell fate towards plasma cell through ERK/ELK1-mediated BACH2 repression. Nature communications 93 29129929
2002 Epidermal growth factor-mediated activation of the ETS domain transcription factor Elk-1 requires nuclear calcium. The Journal of biological chemistry 93 11971908
1999 Stimulation of Elk1 transcriptional activity by mitogen-activated protein kinases is negatively regulated by protein phosphatase 2B (calcineurin). The Journal of biological chemistry 93 10329725
2011 DJ-1 modulates the expression of Cu/Zn-superoxide dismutase-1 through the Erk1/2-Elk1 pathway in neuroprotection. Annals of neurology 92 21796667
2004 SUMOylation regulates nucleo-cytoplasmic shuttling of Elk-1. The Journal of cell biology 82 15210726
2002 Menin uncouples Elk-1, JunD and c-Jun phosphorylation from MAP kinase activation. Oncogene 82 12226747
2020 EGFR activates GDH1 transcription to promote glutamine metabolism through MEK/ERK/ELK1 pathway in glioblastoma. Oncogene 76 32034306
2015 ELK1 is up-regulated by androgen in bladder cancer cells and promotes tumor progression. Oncotarget 74 26342199
1994 elk-1 proteins interact with MAP kinases. Oncogene 74 8208531
2018 MicroRNA-139-3p regulates osteoblast differentiation and apoptosis by targeting ELK1 and interacting with long noncoding RNA ODSM. Cell death & disease 72 30382082
2012 ELK1 uses different DNA binding modes to regulate functionally distinct classes of target genes. PLoS genetics 65 22589737
2010 A common FADS2 promoter polymorphism increases promoter activity and facilitates binding of transcription factor ELK1. Journal of lipid research 64 19546342
2003 Pellino3, a novel member of the Pellino protein family, promotes activation of c-Jun and Elk-1 and may act as a scaffolding protein. Journal of immunology (Baltimore, Md. : 1950) 60 12874243
2010 ERK/ribosomal S6 kinase (RSK) signaling positively regulates death receptor 5 expression through co-activation of CHOP and Elk1. The Journal of biological chemistry 59 21044953
2002 Regulation of the Erk2-Elk1 signaling pathway and megakaryocytic differentiation of Bcr-Abl(+) K562 leukemic cells by Gab2. Blood 59 11830491
2005 Arsenite induces a cell stress-response gene, RTP801, through reactive oxygen species and transcription factors Elk-1 and CCAAT/enhancer-binding protein. The Biochemical journal 58 16008523
2005 Smooth muscle-specific genes are differentially sensitive to inhibition by Elk-1. Molecular and cellular biology 58 16260603
1996 Synergistic interactions between overlapping binding sites for the serum response factor and ELK-1 proteins mediate both basal enhancement and phorbol ester responsiveness of primate cytomegalovirus major immediate-early promoters in monocyte and T-lymphocyte cell types. Journal of virology 57 8970984
2010 Angiotensin II-induced upregulation of AT(1) receptor expression: sequential activation of NF-kappaB and Elk-1 in neurons. American journal of physiology. Cell physiology 56 20554912
2003 Immediate-early gene induction by the stresses anisomycin and arsenite in human osteosarcoma cells involves MAPK cascade signaling to Elk-1, CREB and SRF. Oncogene 54 12660819
2016 A network-based analysis of colon cancer splicing changes reveals a tumorigenesis-favoring regulatory pathway emanating from ELK1. Genome research 52 26860615
1995 Characterization of the Elk-1 ETS DNA-binding domain. The Journal of biological chemistry 49 7890710
2005 PKCalpha expression regulated by Elk-1 and MZF-1 in human HCC cells. Biochemical and biophysical research communications 48 16297876
2018 ELK1-induced upregulation of lncRNA HOXA10-AS promotes lung adenocarcinoma progression by increasing Wnt/β-catenin signaling. Biochemical and biophysical research communications 47 29729275
2017 Tumor-suppressive miRNA-135a inhibits breast cancer cell proliferation by targeting ELK1 and ELK3 oncogenes. Genes & genomics 46 29892795
2013 Signal-dependent Elk-1 target genes involved in transcript processing and cell migration. Biochimica et biophysica acta 46 23711433
2021 Long non-coding RNA ACTA2-AS1 promotes ductular reaction by interacting with the p300/ELK1 complex. Journal of hepatology 45 34953958
2022 ELK1-mediated YTHDF1 drives prostate cancer progression by facilitating the translation of Polo-like kinase 1 in an m6A dependent manner. International journal of biological sciences 43 36439881
2019 ELK1-induced upregulation of lncRNA TRPM2-AS promotes tumor progression in gastric cancer by regulating miR-195/ HMGA1 axis. Journal of cellular biochemistry 43 31104318
2013 ELK1 transcription factor linked to dysregulated striatal mu opioid receptor signaling network and OPRM1 polymorphism in human heroin abusers. Biological psychiatry 43 23702428
2006 Prostaglandin E2 induces fibroblast growth factor 9 via EP3-dependent protein kinase Cdelta and Elk-1 signaling. Molecular and cellular biology 42 16982695
2008 Elk-1, CREB, and MKP-1 regulate Egr-1 expression in gonadotropin-releasing hormone stimulated gonadotrophs. Journal of cellular biochemistry 41 18814180
2000 Expression of immediate early gene pip92 during anisomycin-induced cell death is mediated by the JNK- and p38-dependent activation of Elk1. European journal of biochemistry 40 10903500
2019 PTGER3 induces ovary tumorigenesis and confers resistance to cisplatin therapy through up-regulation Ras-MAPK/Erk-ETS1-ELK1/CFTR1 axis. EBioMedicine 39 30655206
2006 Convergence of the SUMO and MAPK pathways on the ETS-domain transcription factor Elk-1. Biochemical Society symposium 39 16626293
2003 Bcr-Abl regulates protein kinase Ciota (PKCiota) transcription via an Elk1 site in the PKCiota promoter. The Journal of biological chemistry 39 14670960
2000 N-Methyl-D-aspartate receptors and p38 mitogen-activated protein kinase are required for cAMP-dependent cyclase response element binding protein and Elk-1 phosphorylation in the striatum. Neuroscience 38 11113310
2017 NF-κB1, c-Rel, and ELK1 inhibit miR-134 expression leading to TAB1 upregulation in paclitaxel-resistant human ovarian cancer. Oncotarget 37 28206956
2022 GPX4 suppresses ferroptosis to promote malignant progression of endometrial carcinoma via transcriptional activation by ELK1. BMC cancer 36 35962333
2018 Antidepressive effects of targeting ELK-1 signal transduction. Nature medicine 36 29736027
2007 P2X(7) receptor stimulation upregulates Egr-1 biosynthesis involving a cytosolic Ca(2+) rise, transactivation of the EGF receptor and phosphorylation of ERK and Elk-1. Journal of cellular physiology 35 17474086
2011 The ETS family transcription factor ELK-1 regulates induction of the cell cycle-regulatory gene p21(Waf1/Cip1) and the BAX gene in sodium arsenite-exposed human keratinocyte HaCaT cells. The Journal of biological chemistry 34 21642427
2012 The ETS transcription factors ELK1 and GABPA regulate different gene networks to control MCF10A breast epithelial cell migration. PloS one 33 23284628
2022 BCL6 is regulated by the MAPK/ELK1 axis and promotes KRAS-driven lung cancer. The Journal of clinical investigation 32 36377663
2019 Early epigenomic and transcriptional changes reveal Elk-1 transcription factor as a therapeutic target in Huntington's disease. Proceedings of the National Academy of Sciences of the United States of America 31 31744868
2020 A Novel Circular RNA hsa_circRPPH1_015 Exerts an Oncogenic Role in Breast Cancer by Impairing miRNA-326-Mediated ELK1 Inhibition. Frontiers in oncology 30 32670874
2016 miR-1275 inhibits adipogenesis via ELK1 and its expression decreases in obese subjects. Journal of molecular endocrinology 30 27154547
1993 Elk-1 proteins are phosphoproteins and activators of mitogen-activated protein kinase. Cancer research 30 8339245
2019 PSMB8-AS1 activated by ELK1 promotes cell proliferation in glioma via regulating miR-574-5p/RAB10. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 29 31812014
2016 Reduced Ets Domain-containing Protein Elk1 Promotes Pulmonary Fibrosis via Increased Integrin αvβ6 Expression. The Journal of biological chemistry 29 26861876
2011 Both mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinases (ERK) 1/2 and phosphatidylinositide-3-OH kinase (PI3K)/Akt pathways regulate activation of E-twenty-six (ETS)-like transcription factor 1 (Elk-1) in U138 glioblastoma cells. The international journal of biochemistry & cell biology 29 22085529
2003 Ets transcription factors ER81 and Elk1 regulate the transcription of the human presenilin 1 gene promoter. Brain research. Molecular brain research 29 12750007
2020 Arsenite-induced downregulation of occludin in mouse lungs and BEAS-2B cells via the ROS/ERK/ELK1/MLCK and ROS/p38 MAPK signaling pathways. Toxicology letters 28 32683294
2018 Transcriptional activation of miR-320a by ATF2, ELK1 and YY1 induces cancer cell apoptosis under ionizing radiation conditions. International journal of oncology 27 30066913
2006 ERK1/2 regulates ANG II-dependent cell proliferation via cytoplasmic activation of RSK2 and nuclear activation of elk1. American journal of physiology. Cell physiology 27 16723511
2017 NDUFA4L2 is associated with clear cell renal cell carcinoma malignancy and is regulated by ELK1. PeerJ 26 29158991
2012 EGF activates TTP expression by activation of ELK-1 and EGR-1 transcription factors. BMC molecular biology 26 22433566
2022 The SETD8/ELK1/bach1 complex regulates hyperglycaemia-mediated EndMT in diabetic nephropathy. Journal of translational medicine 25 35351142
2021 ELK1‑mediated upregulation of lncRNA LBX2‑AS1 facilitates cell proliferation and invasion via regulating miR‑491‑5p/S100A11 axis in colorectal cancer. International journal of molecular medicine 25 34080639
2022 Sirt7 associates with ELK1 to participate in hyperglycemia memory and diabetic nephropathy via modulation of DAPK3 expression and endothelial inflammation. Translational research : the journal of laboratory and clinical medicine 24 35470010
2021 ELK1-induced upregulation lncRNA LINC02381 accelerates the osteosarcoma tumorigenesis through targeting CDCA4 via sponging miR-503-5p. Biochemical and biophysical research communications 24 33640603
2020 CXXC finger protein 4 inhibits the CDK18-ERK1/2 axis to suppress the immune escape of gastric cancer cells with involvement of ELK1/MIR100HG pathway. Journal of cellular and molecular medicine 24 32715641
2019 ELK1-activated GPC3-AS1/GPC3 axis promotes the proliferation and migration of cervical cancer cells. The journal of gene medicine 23 31168873
2021 Transcription factor ELK1 accelerates aerobic glycolysis to enhance osteosarcoma chemoresistance through miR-134/PTBP1 signaling cascade. Aging 22 33621196
2020 Transcription co-activator P300 activates Elk1-aPKC-ι signaling mediated epithelial-to-mesenchymal transition and malignancy in hepatocellular carcinoma. Oncogenesis 22 32144235
2020 ELK1/lncRNA-SNHG7/miR-2682-5p feedback loop enhances bladder cancer cell growth. Life sciences 22 32898531
2021 The Elk1/MMP-9 axis regulates E-cadherin and occludin in ventilator-induced lung injury. Respiratory research 21 34425812
2016 Silodosin inhibits prostate cancer cell growth via ELK1 inactivation and enhances the cytotoxic activity of gemcitabine. The Prostate 21 26864615
2015 Estrogen receptor ESR1 mediates activation of ERK1/2, CREB, and ELK1 in the corpus of the epididymis. Journal of molecular endocrinology 21 26069273
2004 Androgen inhibition of MAP kinase pathway and Elk-1 activation in proliferating osteoblasts. Journal of molecular endocrinology 21 14766003
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 Elk-1 regulates retinal ganglion cell axon regeneration after injury. Scientific reports 20 36261683
2018 ERK Signaling Controls Innate-like CD8+ T Cell Differentiation via the ELK4 (SAP-1) and ELK1 Transcription Factors. Journal of immunology (Baltimore, Md. : 1950) 20 30068599
2020 Hsa_circRNA_000166 Promotes Cell Proliferation, Migration and Invasion by Regulating miR-330-5p/ELK1 in Colon Cancer. OncoTargets and therapy 19 32606768
2018 Suppression of Elk1 inhibits thyroid cancer progression by mediating PTEN expression. Oncology reports 19 30015900
2007 Elk1 and SRF transcription factors convey basal transcription and mediate glucose response via their binding sites in the human LXRB gene promoter. Nucleic acids research 19 17626048
2022 The autism risk factor CHD8 is a chromatin activator in human neurons and functionally dependent on the ERK-MAPK pathway effector ELK1. Scientific reports 18 36575212
2021 ETS1, ELK1, and ETV4 Transcription Factors Regulate Angiopoietin-1 Signaling and the Angiogenic Response in Endothelial Cells. Frontiers in physiology 18 34381375
2019 Protein inhibitor of activated STAT1 Ser503 phosphorylation-mediated Elk-1 SUMOylation promotes neuronal survival in APP/PS1 mice. British journal of pharmacology 18 30849179
2016 SPAG9 is involved in hepatocarcinoma cell migration and invasion via modulation of ELK1 expression. OncoTargets and therapy 18 27042099
2010 AC3-33, a novel secretory protein, inhibits Elk1 transcriptional activity via ERK pathway. Molecular biology reports 18 20680465
2002 CREB and Elk-1 phosphorylation by metabotropic glutamate receptors in striatal neurons (review). International journal of molecular medicine 18 11744988
2024 ANXA3 interference inactivates ERK/ELK1 pathway to mitigate inflammation and apoptosis in sepsis-associated acute lung injury. Molecular immunology 17 38310670
2023 Guben Xiezhuo Decoction inhibits M1 polarization through the Raf1/p-Elk1 signaling axis to attenuate renal interstitial fibrosis. Journal of ethnopharmacology 17 37716490
2022 Regulation of inflammation and apoptosis by GPR43 via JNK/ELK1 in acute lung injury. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 17 35306578
2020 c-KIT-ERK1/2 signaling activated ELK1 and upregulated carcinoembryonic antigen expression to promote colorectal cancer progression. Cancer science 17 33247506
2018 MicroRNA-873 inhibits colorectal cancer metastasis by targeting ELK1 and STRN4. Oncotarget 17 31289617
2017 Integration of EGFR and LIN-12/Notch Signaling by LIN-1/Elk1, the Cdk8 Kinase Module, and SUR-2/Med23 in Vulval Precursor Cell Fate Patterning in Caenorhabditis elegans. Genetics 17 28954762

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