Affinage

DUSP6

Dual specificity protein phosphatase 6 · UniProt Q16828

Length
381 aa
Mass
42.3 kDa
Annotated
2026-04-28
100 papers in source corpus 42 papers cited in narrative 41 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DUSP6 (MKP-3/Pyst1) is a cytoplasmic dual-specificity phosphatase that functions as a central negative-feedback regulator of ERK1/2 MAP kinase signaling while also acting on non-canonical substrates including Drp1 and SMAD2. DUSP6 selectively binds ERK2 through its N-terminal domain, which allosterically activates the catalytic domain by inducing closure of the Asp262 general-acid loop; it does not bind or dephosphorylate JNK, p38, or ERK5 (PMID:9596579, PMID:8670865, PMID:10048930, PMID:18280112). DUSP6 transcription is induced by ERK1/2 via ETS2 binding and CIC derepression at the DUSP6 promoter, while DUSP6 protein turnover is controlled by ERK1/2- and mTOR-dependent phosphorylation of S159/S197 targeting it for proteasomal degradation, SUMO1/2/3-ylation at K234 that stabilizes the protein, and ubiquitin ligases FBXO31, TRIM7, and TRIM65 (PMID:18321244, PMID:33103082, PMID:15632084, PMID:18223677, PMID:32232156, PMID:34686346). Beyond ERK1/2 inactivation, DUSP6 dephosphorylates Drp1-S616 to restrain mitochondrial fission, scaffolds a CK2–progesterone receptor B transcriptional complex independently of phosphatase activity, interacts with FOXO1 to promote hepatic gluconeogenesis, and regulates DNA damage repair by facilitating phospho-DNAPKcs recruitment to double-strand breaks (PMID:32232156, PMID:23921636, PMID:24722245, PMID:34792128).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 High

    Identification of DUSP6 as a cytoplasmic, ERK-selective dual-specificity phosphatase established that a dedicated cytosolic inactivator exists for ERK but not JNK or p38, defining the core substrate specificity of the enzyme.

    Evidence In vitro phosphatase assays, co-immunoprecipitation with endogenous MAP kinase, and subcellular fractionation in COS-1/COS-7 cells and sympathetic neurons

    PMID:8626780 PMID:8670865

    Open questions at the time
    • Structural basis of ERK selectivity unknown
    • Mechanism of catalytic activation by ERK not addressed
  2. 1998 High

    Demonstration that ERK2 binding allosterically activates DUSP6 catalysis through the N-terminal domain—independently of ERK2 kinase activity—revealed a substrate-induced activation mechanism and explained why the Sevenmaker ERK2 mutant escapes DUSP6 control.

    Evidence In vitro binding and enzymatic activity assays with purified recombinant proteins; Sevenmaker mutant ERK2 analysis

    PMID:9596579

    Open questions at the time
    • Atomic-resolution mechanism of allosteric activation not yet resolved
    • In vivo relevance of substrate-induced activation not tested
  3. 1999 High

    The crystal structure of the DUSP6 catalytic domain showed that ERK2 binding induces closure of the Asp262 general-acid loop, switching the enzyme from a low- to high-activity conformation, providing the structural basis for substrate-induced activation.

    Evidence X-ray crystallography at 2.35 Å; kinetic analysis; D262 mutagenesis

    PMID:10048930

    Open questions at the time
    • Full-length DUSP6 structure with ERK2 not determined
    • Dynamics of loop closure not characterized
  4. 2000 High

    Discovery that nitric oxide destabilizes DUSP6 mRNA without affecting catalytic activity introduced post-transcriptional regulation as a mechanism controlling DUSP6 abundance independently of transcription.

    Evidence NO donor treatment with mRNA stability assays and phosphatase activity assays in endothelial cells

    PMID:10846176

    Open questions at the time
    • RNA-binding factor mediating NO-induced mRNA destabilization not identified
  5. 2005 High

    Identification of ERK2-mediated phosphorylation of DUSP6 at S159/S197 promoting proteasomal degradation revealed a paradoxical positive-feedback loop whereby ERK destroys its own inhibitor, adding a protein-stability layer to MAPK signal tuning.

    Evidence In vitro ERK2 phosphorylation of GST-MKP-3; tetracycline-inducible serine mutant cell lines; proteasome inhibitor experiments

    PMID:15632084

    Open questions at the time
    • Identity of the E3 ubiquitin ligase mediating ERK-directed degradation not yet known at this point
    • Role of mTOR in S159 phosphorylation not yet distinguished
  6. 2008 High

    Three contemporaneous advances established (1) mTOR-dependent phosphorylation of S159 as a second input for DUSP6 degradation, (2) ERK1/2-ETS2-dependent transcriptional induction of DUSP6 completing the negative-feedback circuit, and (3) Dusp6-knockout mouse phenotypes confirming that DUSP6 is the dominant cytoplasmic ERK1/2 phosphatase in vivo across multiple tissues.

    Evidence mTOR/PI3K inhibitors with S159 mutagenesis; ChIP for ETS2 at DUSP6 promoter with reporter assays; Dusp6-KO mouse with tissue-level phospho-ERK analysis, cardiac phenotyping, and MEF assays

    PMID:18223677 PMID:18321244 PMID:18753132 PMID:18848526

    Open questions at the time
    • Relative contribution of mTOR versus ERK to S159 phosphorylation in different cell types unclear
    • CIC-dependent repression not yet integrated into the transcriptional model
  7. 2009 High

    Identification of BCI as an allosteric inhibitor that blocks ERK2-induced catalytic activation provided the first tool compound for pharmacological DUSP6 inhibition and validated the allosteric activation mechanism in vivo.

    Evidence Transgenic zebrafish chemical screen; docking simulations; in vitro enzymatic assay; FGF target gene expression in zebrafish

    PMID:19578332

    Open questions at the time
    • BCI selectivity across the DUSP family not fully characterized
    • No co-crystal structure of BCI with DUSP6
  8. 2011 High

    Parallel discoveries showed that DUSP6 mRNA stability is regulated by TTP, PUM2, and hypoxia/HIF-1 via the 3′UTR, and that DUSP6 induction in oligodendrocytes modulates AMPA receptor permeability and excitotoxic death, extending DUSP6 function to post-transcriptional regulation and neuronal injury.

    Evidence 3′UTR reporter and mRNA half-life assays; DUSP6 knockdown and overexpression in oligodendrocytes with electrophysiology and calcium imaging

    PMID:20665674 PMID:21300799

    Open questions at the time
    • Direct binding of TTP/PUM2 to DUSP6 3′UTR not shown by CLIP
    • Mechanism linking DUSP6 to AMPA receptor channel properties not defined
  9. 2012 High

    Multiple studies in 2012 established caspase-3 cleavage of DUSP6 during apoptosis, miR-181a as a direct repressor of DUSP6 controlling T cell activation in aging, and ERK-mediated DUSP6 degradation in liver as a mechanism coupling insulin signaling to gluconeogenesis.

    Evidence Caspase-3 cleavage assays with fragment characterization; miR-181a reconstitution and siRNA in elderly CD4+ T cells; cycloheximide chase with S159/S197 mutagenesis in hepatocytes

    PMID:22504224 PMID:22521266 PMID:23023500

    Open questions at the time
    • Physiological role of caspase-3-generated DUSP6 fragments unclear
    • Whether miR-181a regulation is T cell–specific not established
  10. 2013 High

    Discovery that DUSP6 scaffolds a CK2–PR-B complex for Ser81 phosphorylation at the Wnt1 enhancer, independently of its phosphatase activity, revealed a non-catalytic function for DUSP6 in transcriptional regulation; separately, DUSP6 depletion was shown to activate the DNA damage response pathway.

    Evidence Domain-mapping pulldowns, ChIP at Wnt1 enhancer, and transcriptional reporters for scaffold function; phosphoproteomic profiling and DDR marker analysis upon siRNA/shRNA knockdown

    PMID:23839489 PMID:23921636

    Open questions at the time
    • Structural basis of DUSP6 scaffold function unknown
    • Whether DUSP6 directly dephosphorylates DDR substrates or acts indirectly through ERK not resolved
  11. 2014 High

    Mapping of the DUSP6–FOXO1 interaction and demonstration that DUSP6 phosphatase activity promotes FOXO1 nuclear translocation and gluconeogenesis established DUSP6 as a metabolic regulator in the liver.

    Evidence Mutant adenoviral constructs for domain mapping; co-IP; G6Pase reporter and glucose output assays; in vivo liver rescue

    PMID:22848439 PMID:24722245

    Open questions at the time
    • Whether DUSP6 directly dephosphorylates FOXO1 at ERK sites not shown biochemically
    • Contribution relative to other ERK phosphatases in hepatic gluconeogenesis unclear
  12. 2018 High

    Two studies revealed that PKN2 phosphorylates and activates DUSP6 to suppress macrophage M2 polarization via IL-4/IL-10, and that DUSP6 is required for glycolytic commitment in T cells upon TCR/CD28 co-stimulation while restraining TFH differentiation, broadening DUSP6's role to immune cell metabolism and polarization.

    Evidence Co-IP and kinase/phosphatase activity assays with ChIP-qPCR for PKN2 axis; DUSP6-KO T cells with metabolic flux analysis and in vivo immunization

    PMID:29368606 PMID:30087184

    Open questions at the time
    • PKN2 phosphorylation sites on DUSP6 not mapped
    • Mechanism linking DUSP6 to phosphofructokinase induction not defined
  13. 2020 High

    Identification of Drp1-S616 as a non-canonical DUSP6 substrate and of K234 SUMOylation as a stabilizing modification revealed that DUSP6 directly regulates mitochondrial fission dynamics under oxidative stress through a SENP1-dependent deSUMOylation–degradation axis; separately, CIC was identified as a direct transcriptional repressor of DUSP6 whose nuclear export by p90RSK completes the ERK negative-feedback loop.

    Evidence In vitro Drp1-S616 dephosphorylation assay; K234R mutagenesis; SENP1 manipulation; brain ischemia/reperfusion model; ChIP for CIC at DUSP6 CREs; CIC phosphorylation and 14-3-3 interaction assays

    PMID:32232156 PMID:33103082

    Open questions at the time
    • Whether DUSP6 dephosphorylates Drp1 in a complex with ERK or independently unclear
    • Full repertoire of CIC-regulated DUSP family members not defined
  14. 2021 High

    Multiple 2021 studies identified three E3 ubiquitin ligases (FBXO31, TRIM7, TRIM65) that target DUSP6 for proteasomal degradation, demonstrated DUSP6 as a critical effector of NKX2-1 tumor suppression in lung adenocarcinoma, showed DUSP6 facilitates DNAPKcs-mediated DNA repair and radiosensitization in GBM, and linked DUSP6 deficiency to enhanced epithelial barrier integrity and colitis resistance through altered metabolism and microbiota.

    Evidence Co-IP and ubiquitylation assays for each E3 ligase; NKX2-1/DUSP6 epistasis in xenograft and mouse models; DNAPKcs/γH2AX foci analysis with BCI and genetic inhibition in orthotopic GBM; DUSP6-CRISPR Caco-2 and Dusp6-KO mice with metabolic flux and fecal transplant

    PMID:30850165 PMID:33146694 PMID:34475393 PMID:34686346 PMID:34689179 PMID:34792128 PMID:34818535

    Open questions at the time
    • Relative importance of FBXO31 vs. TRIM7 vs. TRIM65 in different tissues not compared
    • Whether nuclear DUSP6 in GBM acts on DNAPKcs directly or via ERK unknown
    • Microbiota species mediating colitis protection not fully characterized
  15. 2022 High

    DUSP6 was found to maintain p38 activity in neutrophils by downregulating pERK and p38-targeting phosphatases DUSP1/DUSP16, driving myocardial injury post-MI; separately, DUSP6 was implicated in JAK2-inhibitor resistance in myeloproliferative neoplasms through modulation of S6 and JAK-STAT signaling, and paralog epistasis screens showed that dual DUSP4/DUSP6 loss selectively kills NRAS/BRAF-mutant cancers.

    Evidence Neutrophil-specific DUSP6 KO and bone marrow transplant in MI models; scRNA-seq and PDX models for MPN; CRISPR paralog library screen across cancer cell lines

    PMID:34857952 PMID:36335128 PMID:36581736

    Open questions at the time
    • Mechanism by which DUSP6 downregulates DUSP1/DUSP16 in neutrophils not defined
    • Direct DUSP6 substrates in MPN cells not identified
    • Therapeutic window for dual DUSP4/DUSP6 targeting not assessed in vivo
  16. 2024 High

    DUSP6 was identified as a positive regulator of HER3 expression that mediates HER2-inhibitor tolerance in breast cancer via the neuregulin–HER3 axis, positioning DUSP6 inhibition as a strategy to prevent therapy resistance.

    Evidence Transcriptional profiling of drug-tolerant cells; DUSP6 overexpression and genetic targeting; neuregulin-HER3 pathway analysis; in vivo brain metastasis model

    PMID:38886591

    Open questions at the time
    • Mechanism by which DUSP6 upregulates HER3 transcription not elucidated
    • Whether this axis operates in other HER2+ cancer types untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full-length DUSP6–ERK2 co-crystal structure, the complete inventory of non-ERK substrates and their relative kinetic parameters, the tissue-specific hierarchy among the multiple E3 ligases and post-translational modifications controlling DUSP6 stability, and the mechanistic basis for DUSP6's nuclear functions in DNA repair and transcriptional scaffolding.
  • No full-length DUSP6–ERK2 co-structure available
  • Kinetic parameters for Drp1, SMAD2, and other non-ERK substrates not compared
  • Tissue-specific relative contributions of FBXO31, TRIM7, TRIM65, SUMOylation, and caspase-3 cleavage to DUSP6 turnover uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 2 R-HSA-73894 DNA Repair 2 R-HSA-1852241 Organelle biogenesis and maintenance 1
Partners
CSNK2A1DNL1FBXO31FOXO1MAPK1MAPK3PGRPKN2

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 MKP-3/DUSP6 is catalytically activated by direct binding to ERK2; this activation requires the noncatalytic N-terminus of MKP-3 and is independent of ERK2 kinase activity. The gain-of-function Sevenmaker ERK2 mutant D319N does not bind or activate MKP-3, and JNK/SAPK or p38 do not bind or activate MKP-3. In vitro binding assay with purified proteins; enzymatic activity assays; mutant ERK2 analysis Science High 9596579
1996 Pyst1/DUSP6 is a cytoplasmic dual-specificity phosphatase that selectively dephosphorylates and inactivates ERK (MAP kinase) but has very low activity toward JNK/SAPK or p38 in vitro and in vivo; it forms a physical complex with endogenous MAP kinase in cells. In vitro phosphatase assay; co-immunoprecipitation of endogenous MAP kinase; transfection in COS-1 cells; subcellular fractionation/localization The EMBO Journal High 8670865
1996 MKP-3/DUSP6 is a cytosolic protein (excluded from the nucleus) that suppresses ERK2 phosphorylation and enzymatic activation by mitogens when expressed in COS-7 cells. Epitope-tagged subcellular localization in sympathetic neurons; COS-7 cell transfection; ERK2 phosphorylation assay The Journal of Biological Chemistry High 8626780
1999 Crystal structure of the Pyst1/DUSP6 catalytic domain (2.35 Å) reveals a PTPase fold with shallow active site and distorted geometry; ERK2 binding induces closure of the Asp262 loop over the active site, switching DUSP6 from a low- to high-activity form. Mutation of Asp262 abolishes catalysis only in the ERK2-stimulated (high-activity) conformation. X-ray crystallography; kinetic analysis with pNPP substrate; site-directed mutagenesis (D262); in vitro ERK2-dependent activation assay Nature Structural Biology High 10048930
2005 ERK2 phosphorylates DUSP6/MKP-3 on serines 159 and 197, promoting its proteasomal degradation; this constitutes a positive feedback by which ERK1/2 enhance their own signaling by degrading their primary cytosolic inactivator. Phosphorylation at these sites does not affect DUSP6 catalytic activity. In vitro ERK2 phosphorylation of GST-MKP-3 fusion proteins; tetracycline-inducible cell clones with single and double serine mutants; proteasome inhibitor experiments; half-life measurements Molecular and Cellular Biology High 15632084
2008 DUSP6/MKP-3 is transcriptionally induced by FGF signaling via an ERK1/2-dependent mechanism; transcriptional activation requires a conserved Ets-factor binding site in the DUSP6 promoter, and the Ets2 protein (a known ERK target) binds to the endogenous DUSP6 promoter. Pharmacological inhibitors of ERK pathway; murine DUSP6 promoter-EGFP reporter in chicken neural plate; ChIP for Ets2 at endogenous DUSP6 promoter; site-directed mutation of Ets-binding site The Biochemical Journal High 18321244
2007 DUSP6 specifically binds ERK1/2 (in yeast two-hybrid and human cells) but fails to bind ERK5; recombinant ERK2 induces catalytic activation of DUSP6 but ERK5 cannot; ectopic DUSP6 dephosphorylates ERK2 but not ERK5; DUSP6 blocks MEK1-driven ERK1/2 signaling but not MEK5-driven ERK5 signaling. Yeast two-hybrid; co-immunoprecipitation; in vitro catalytic activation assay; cotransfection dephosphorylation assay; GAL4-ELK1 and GAL4-MEF2D transcription reporter assays Cellular Signalling High 18280112
2008 Dusp6 knockout mice show increased basal ERK1/2 phosphorylation in heart, spleen, kidney, brain, and fibroblasts, but no change in ERK5, p38, or JNK activation; loss of Dusp6 leads to larger hearts with greater myocyte proliferation during embryonic/early postnatal development, cardiac hypercellularity, protection against hypertrophic cardiomyopathy, and reduced apoptosis in MEFs. Targeted gene disruption (knockout mouse); immunoblotting for phospho-ERK1/2 in multiple tissues; cardiac histology; flow cytometry for proliferation and apoptosis; pressure overload and MI models The Journal of Biological Chemistry High 18753132
2008 The PI3K/mTOR pathway contributes to DUSP6 phosphorylation and proteasomal degradation induced by growth factors; serine 159 within DUSP6 is identified as the specific mTOR pathway target; a basal MEK activity is required for the mTOR-mediated phosphorylation to occur. Pharmacological inhibitors of PI3K and mTOR; mTOR-specific agonists (amino acids, insulin/IGF-1); site-directed mutagenesis of S159; inducible cell expression system Oncogene High 18223677
2009 BCI [(E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one] is an allosteric inhibitor of Dusp6 that inhibits catalytic activation of Dusp6 by ERK2 substrate binding; docking simulations predict an allosteric binding site within the phosphatase domain; in vivo, BCI blocks Dusp6 activity and enhances FGF target gene expression in zebrafish embryos. Transgenic zebrafish chemical screen; docking simulations; in vitro Dusp6 activity assay; FGF target gene expression analysis in zebrafish Nature Chemical Biology High 19578332
2012 miR-181a directly represses DUSP6 expression; age-associated decline in miR-181a increases DUSP6 protein levels in naive CD4+ T cells, causing defective TCR-induced ERK phosphorylation; reconstitution of miR-181a or siRNA knockdown of DUSP6 improved T cell activation, proliferation, and TH1 differentiation. miR-181a reconstitution in elderly T cells; DUSP6 siRNA knockdown; allosteric DUSP6 inhibitor (BCI); flow cytometry for activation markers; proliferation assays Nature Medicine High 23023500
2011 mRNA stability of DUSP6 is regulated post-transcriptionally by MEK/ERK signaling in a 3'UTR-dependent manner; Tristetraprolin (TTP) and PUM2 reduce DUSP6 mRNA levels via the 3'UTR; hypoxia increases DUSP6 mRNA stability in a HIF-1-dependent and basal ERK activity-requiring manner. Luciferase reporter with DUSP6 3'UTR; mRNA half-life measurement with cycloheximide; MEK inhibitors; hypoxia/HIF-1 manipulation; TTP and PUM2 overexpression Journal of Cellular Physiology High 20665674
2012 Caspase-3 cleaves DUSP6/MKP3 at the interdomain linker region during apoptosis, generating N-terminal and C-terminal fragments with differential abilities to regulate ERK1/2 nuclear/cytosolic localization and activity; full-length MKP3 protein levels decrease upon apoptotic stimulation in a caspase-dependent manner. Caspase-3 cleavage assay in vitro and in cells; analysis of MKP3 fragments by immunoblot; ERK1/2 subcellular localization by fractionation/imaging; apoptotic stimulation Journal of Molecular Biology High 22504224
2013 DUSP6 interacts with progesterone receptor B (PR-B) via a common docking (CD) domain in PR-B; this interaction enables CK2-dependent phosphorylation of PR-B on Ser81, required for formation of a PR-B/DUSP6/CK2 transcriptional complex at the Wnt1 enhancer and STAT5A gene; DUSP6 acts as a scaffold (not as a phosphatase) in this context. Binding studies (pulldown); CD domain mutation of PR-B; co-IP; ChIP at Wnt1 enhancer; transcriptional reporter assays; JAK/STAT inhibition Nucleic Acids Research High 23921636
2020 DUSP6 dephosphorylates Drp1-S616 (independently of its known substrates ERK1/2), keeping Drp1-S616 phosphorylation low under normal conditions; DUSP6 is SUMOylated at K234 by SUMO1/2/3, and this SUMOylation stabilizes DUSP6. During oxidative stress, SENP1 is upregulated, causing deSUMOylation and proteasomal degradation of DUSP6, leading to Drp1-S616 hyperphosphorylation, mitochondrial fragmentation, and apoptosis; SUMOylation-deficient DUSP6-K234R mutant fails to protect cells. In vitro dephosphorylation assay (Drp1-S616 as substrate); co-IP; site-directed mutagenesis (K234R); SENP1 manipulation; mitochondrial fragmentation imaging; apoptosis assays; in vivo brain ischemia/reperfusion model Science Advances High 32232156
2018 PKN2 phosphorylates and activates DUSP6 through direct association; activated DUSP6 then suppresses ERK1/2 phosphorylation, inhibiting CREB/Elk-1-driven expression of IL-4 and IL-10 in colon cancer cells, thereby suppressing M2 macrophage polarization. Co-IP; kinase activity assay for PKN2; DUSP6 catalytic activity assay; ChIP-qPCR; siRNA knockdown; in vivo xenograft model Molecular Cancer High 29368606
2018 DUSP6 regulates TCR signaling to influence T cell metabolism: DUSP6-knockout T cells show enhanced JNK and p38 phosphorylation but impaired glycolysis; DUSP6 is necessary for phosphofructokinase induction and metabolic commitment to glycolysis upon CD28 co-stimulation; DUSP6 restrains TFH cell differentiation by inhibiting IL-21 production through a fatty acid oxidation-linked mechanism. DUSP6 knockout mice; DUSP6-/-OTII transgenic mice; in vitro T cell differentiation assays; JNK/p38 inhibitors; metabolic flux analysis; immunization experiments PNAS High 30087184
2020 CIC (transcriptional repressor) directly represses DUSP6 transcription by binding three cis-regulatory elements (CREs) in the DUSP6 promoter; p90RSK (a downstream ERK1/2 target) phosphorylates CIC at S173 and S301, creating a 14-3-3 recognition motif that drives nuclear export of CIC and derepresses DUSP6 transcription, completing an ERK1/2/p90RSK/CIC/DUSP6 negative feedback circuit. ChIP for CIC at DUSP6 CREs; promoter reporter assays; CIC phosphorylation assay; 14-3-3 interaction assay; CIC nuclear/cytoplasmic localization assay; CIC-DUX4 fusion analysis iScience High 33103082
2021 Dual inactivation of DUSP4 and DUSP6 selectively impairs growth in NRAS- and BRAF-mutant cancer cells through hyperactivation of MAPK signaling; cells resistant to MAPK pathway therapeutics become cross-sensitized to DUSP4/DUSP6 dual perturbation. CRISPR paralog knockout library screen across cancer cell lines; genetic epistasis with MAPK pathway mutations; drug resistance combination experiments Nature Genetics High 34857952
2022 DUSP6 is transcriptionally activated by p38-C/EBPβ signaling in neutrophils and acts as an effector maintaining p-p38 activity by downregulating pERK and the p38-targeting phosphatases DUSP1/DUSP16; Dusp6-deficient neutrophils cause less myocardial damage post-MI, improving cardiac outcomes. Rat Dusp6 nonsense mutation model; neutrophil-cardiomyocyte co-culture; bone marrow transplantation; neutrophil-specific DUSP6 KO mice; mechanistic signaling analysis Nature Communications High 36335128
2022 Ectopic DUSP6 expression mediates JAK2-inhibitor resistance; DUSP6 inhibits S6 and JAK-STAT signaling and reduces inflammatory cytokine production; DUSP6 perturbation inhibits RSK1, identified as a co-dependent candidate; pharmacological DUSP6 targeting suppresses disease in Jak2V617F and MPLW515L MPN mouse models. Single-cell RNA sequencing; DUSP6 ectopic expression in PDX models; pharmacological DUSP6 inhibition; MPN mouse models; RSK1 co-dependence analysis Nature Cancer High 36581736
2021 Loss of the ubiquitin ligase FBXO31 stabilizes DUSP6, suppressing ERK signaling and activating PI3K-AKT signaling cascade; CRL1FBXO31 promotes ubiquitylation-mediated degradation of DUSP6; in prostate cancer, this axis drives tumor development reversible by BCI (DUSP6 inhibitor) which suppresses AKT activation. Co-IP; ubiquitylation assay; FBXO31 depletion stabilizing DUSP6; orthotopic mouse prostate cancer model; BCI treatment; AKT/ERK signaling analysis Cell Reports High 34686346
2000 Nitric oxide (NO) down-regulates MKP-3/DUSP6 by destabilizing its mRNA, reducing protein levels; this protects ERK1/2 from TNFα-induced dephosphorylation in endothelial cells, preventing Bcl-2 proteolysis and apoptosis; NO has no effect on DUSP6 catalytic activity, indicating the regulation is exclusively at the mRNA level. NO donor treatment; MKP-3 mRNA stability assay; MKP-3 overexpression; phosphatase activity assay; Bcl-2/cytochrome c immunoblotting The Journal of Biological Chemistry High 10846176
2003 Adenovirus-mediated reintroduction of DUSP6/MKP-3 into pancreatic cancer cells reduces phosphorylated ERK in a dose-dependent manner and suppresses cell growth; exogenous DUSP6 expression induces apoptosis as shown by flow cytometry. Adenovirus-mediated gene reintroduction; immunoblotting for p-ERK; cell growth assay; flow cytometry and immunocytochemistry for apoptosis The American Journal of Pathology High 12759238
2014 MKP-3/DUSP6 interacts with FOXO1 (residues 200-260 of MKP-3 bind residues 360-456 of FOXO1); MKP-3 phosphatase activity is not required for this interaction but is essential for FOXO1 nuclear translocation and MKP-3-promoted gluconeogenesis (G6Pase gene expression); ERK phosphorylation-deficient FOXO1 mutant loses interaction with MKP-3. Mutant adenoviral constructs for MKP-3 and FOXO1; co-IP; G6Pase reporter; glucose output assay; in vivo liver rescue experiments Diabetes (via earlier PLOS ONE mapping paper 2012) High 22848439 24722245
2021 DUSP6 deficiency in the colon enhances epithelial barrier integrity and alters glucose metabolism (increased mitochondrial oxygen consumption, decreased glycolysis) in Caco-2 cells; Dusp6-KO mice resist DSS-induced dysbiosis and colitis, with transferable protection via fecal microbiota transplantation. DUSP6 CRISPR mutation in Caco-2 cells; Dusp6-KO mice; DSS colitis model; metabolic flux analysis; co-housing and fecal microbiota transplantation; culturomics and mono-colonization Cell Reports High 34818535
2011 DUSP6 is up-regulated in oligodendrocytes upon AMPA receptor activation; blocking DUSP6 expression enhances ERK1/2 phosphorylation and significantly reduces AMPA receptor-induced oligodendrocyte death; DUSP6 overexpression increases AMPA receptor-induced inward currents and calcium overload, suggesting DUSP6 regulates glutamate receptor permeability. Microarray and qPCR in oligodendrocyte cultures and optic nerves; DUSP6 knockdown; ERK phosphorylation assay; electrophysiology (AMPA-induced currents); calcium imaging; cytochrome c/mitochondrial depolarization assays The Journal of Biological Chemistry High 21300799
2012 Ischemia/reperfusion induces endothelial MKP-3/DUSP6 expression, which inactivates ERK1/2 and impairs eNOS expression and NO production; siRNA knockdown of MKP-3 restores eNOS and NO; MKP-3-mediated ERK inactivation promotes HDAC1 recruitment to the eNOS promoter, causing histone deacetylation and eNOS repression. HUVECs I/R model; siRNA knockdown; constitutively active ERK plasmid transfection; HDAC inhibitor; ChIP for HDAC1 at eNOS promoter; NO measurement PLoS One High 22848708
2013 DUSP6 depletion activates CHEK2 and p38, and elevates phospho-H2AX, ATM, and CHEK2, identifying DUSP6 as a regulator of the DNA damage response (DDR) pathway; DUSP6 depletion reduces cancer cell viability and increases sensitivity to EGFR inhibitors and cytotoxic agents in vitro and in xenografts. siRNA and shRNA knockdown; phosphoproteomic analysis; DDR marker immunoblotting (γH2AX, p-ATM, p-CHEK2); xenograft mouse model; viability assays British Journal of Cancer High 23839489
2021 DUSP6 inhibition (BCI or genetic) radiosensitizes primary and relapse GBM cells by inhibiting recruitment of phosphorylated DNAPKcs (PRKDC) to DSBs, subsequently reducing γH2AX and 53BP1 recruitment, thus impairing DNA repair; nuclear localization of DUSP6 found in primary and recurrent GBM biopsies and cell lines. BCI pharmacological inhibition; genetic DUSP6 inhibition; clonogenic survival assays; DNAPKcs/γH2AX/53BP1 foci analysis; orthotopic mouse GBM model; direct localization (nuclear vs. cytoplasmic) in patient samples Journal of Cell Science High 34792128
2019 TRIM7 ubiquitinates DUSP6 and promotes its polyubiquitination and proteasomal degradation, thereby activating p38 signaling and promoting HCC cell proliferation; DUSP6 overexpression abolishes the TRIM7-driven p38 activation and proliferation. Co-IP; ubiquitylation assay; TRIM7 and DUSP6 overexpression/knockdown; p38 activity assay; SB203580 p38 inhibitor rescue Biochemical and Biophysical Research Communications Medium 30850165
2021 TRIM65 ubiquitinates DUSP6, promoting ERK1/2 activation; C-myc induced by ERK1/2 then activates TRIM65 transcription via its promoter, forming a positive feedback loop in endometrial stromal cells; DUSP6 overexpression reverses TRIM65-driven ERK1/2/C-myc activation and invasion. Co-IP; ubiquitylation assay; dual luciferase; ChIP for C-myc at TRIM65 promoter; Transwell invasion assay; in vivo endometriosis mouse model The Journal of Clinical Endocrinology and Metabolism Medium 33146694
2021 NKX2-1 transcription factor induces DUSP6 expression to suppress ERK activity in lung adenocarcinoma; DUSP6 is necessary for NKX2-1-mediated inhibition of tumor progression in vivo; DUSP6 expression is sufficient to inhibit RAS-driven LUAD. NKX2-1 re-introduction in NKX2-1-silenced LUAD cells; DUSP6 genetic manipulation; xenograft and genetic mouse models; ERK activity assays Oncogene High 34689179
2021 DUSP6 deficiency enhances osteoclastogenesis prevention via ERK2 and SMAD2 signaling; DUSP6 directly dephosphorylates SMAD2, modulating NFATC1 nuclear translocation to regulate osteoclast differentiation; miR-181a is an upstream regulator of DUSP6 in this context. DUSP6 overexpression/siRNA knockdown; ERK2-deficient bone marrow macrophages; immunoprecipitation confirming DUSP6 direct modification of SMAD2 phosphorylation; NFATC1 nuclear localization assay; in vivo BCI treatment Cell Death & Disease Medium 34475393
2024 DUSP6 is a positive regulator of HER3 expression; its impact on HER2 inhibitor tolerance is mediated by the neuregulin-HER3 axis; DUSP6 overexpression confers apoptosis resistance in HER2+ breast cancer and its pharmacological blockade prevents therapy tolerance development; DUSP6 targeting synergizes with HER2i combination therapies in vivo. Transcriptional profiling of drug-tolerant cells; DUSP6 overexpression/genetic targeting; neuregulin-HER3 pathway analysis; in vivo brain metastasis model; pharmacological DUSP6 inhibition EMBO Molecular Medicine High 38886591
2022 DUSP6 interacts with JNK (as shown by enhanced DUSP6-JNK interaction upon lncRNA TCONS_00145741 knockdown), and this interaction reduces JNK phosphorylation, shifting microglia toward M2 differentiation; lncRNA TCONS_00145741 impairs this interaction to promote M1 microglia polarization. RNA pull-down; RNA immunoprecipitation; RNA FISH + immunofluorescence; immunoblot for JNK phosphorylation; flow cytometry for M1/M2 markers; in vivo ICH model Frontiers in Cell and Developmental Biology Medium 35127692
2019 Dusp6 attenuates Ras/MAPK (ERK) signaling during zebrafish heart regeneration; suppressing Dusp6 by BCI or gene inactivation increases cardiomyocyte proliferation, coronary angiogenesis, and reduces fibrosis after ventricular resection; in rat primary cardiomyocytes, NRG1-stimulated proliferation is enhanced by DUSP6 chemical inhibition. Zebrafish dusp6 mutants; BCI chemical inhibition; ventricular resection model; cardiomyocyte proliferation assay; coronary angiogenesis imaging; rat primary cardiomyocyte NRG1 stimulation Development High 29444893
2019 The Met62Ile substitution in DUSP6 from DBA/2J mice reduces the interaction between DUSP6 and ERK, resulting in increased ERK phosphorylation and ERK activity; myoblasts expressing Met62Ile DUSP6 are insensitive to BCI-induced proliferation, while canonical DUSP6-expressing myoblasts show enhanced proliferation with BCI. Whole-genome and RNA sequencing; Co-IP/interaction assay; ERK phosphorylation measurement; BCI sensitivity assay in myoblasts Human Molecular Genetics Medium 30289454
2014 MEF2D functions as a p38MAPK-dependent transcriptional repressor of DUSP6 in skeletal myoblasts; MEF2A/D heterodimer has divergent roles in regulating DUSP6 in cardiac versus skeletal myogenic lineages, as identified by ChIP-exo and MEF2A siRNA depletion. ChIP-exo in cardiomyocytes and myoblasts; RNA-seq in MEF2A-depleted cells; MEF2A/D siRNA; p38MAPK inhibition Nucleic Acids Research Medium 25217591
2008 Feedback regulation of DUSP6 transcription by MAPK1/ERK2 via ETS2: the DUSP6 intron 1 has promoter activity dependent on ERK activity and a consensus ETS transcription factor binding site; ETS2 specifically associates with the intron 1 region, linking MAPK1 activity to DUSP6 transcription. Luciferase promoter activity assay; MEK/ERK inhibitors; ETS2 binding site mutagenesis; ChIP for ETS2 at DUSP6 intron 1 Biochemical and Biophysical Research Communications High 18848526
2012 MEK/ERK pathway mediates insulin-promoted degradation of MKP-3/DUSP6 protein in liver cells; MEK inhibitor slows MKP-3 protein degradation; double serine mutation (S159/S197) renders MKP-3 resistant to insulin- and constitutively active MEK-induced degradation; reduced MKP-3 stability (via ERK activation) decreases G6Pase expression and glucose output. Cycloheximide chase assay; MEK inhibitor; constitutively active MEK; serine-to-alanine mutagenesis; G6Pase mRNA and glucose output assay Molecular and Cellular Endocrinology High 22521266

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Catalytic activation of the phosphatase MKP-3 by ERK2 mitogen-activated protein kinase. Science (New York, N.Y.) 440 9596579
1996 Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase. The EMBO journal 359 8670865
1996 MKP-3, a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase. The Journal of biological chemistry 321 8626780
2012 Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity. Nature medicine 296 23023500
2009 Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages. Nature chemical biology 208 19578332
2013 Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. American journal of human genetics 200 23643382
2003 Potential tumor suppressive pathway involving DUSP6/MKP-3 in pancreatic cancer. The American journal of pathology 189 12759238
2008 Negative-feedback regulation of FGF signalling by DUSP6/MKP-3 is driven by ERK1/2 and mediated by Ets factor binding to a conserved site within the DUSP6/MKP-3 gene promoter. The Biochemical journal 164 18321244
2010 Dual specificity phosphatase 6 (DUSP6) is an ETS-regulated negative feedback mediator of oncogenic ERK signaling in lung cancer cells. Carcinogenesis 160 20097731
2008 DUSP6 (MKP3) null mice show enhanced ERK1/2 phosphorylation at baseline and increased myocyte proliferation in the heart affecting disease susceptibility. The Journal of biological chemistry 150 18753132
2003 Negative feedback regulation of FGF signaling levels by Pyst1/MKP3 in chick embryos. Current biology : CB 150 12814546
1999 Crystal structure of the MAPK phosphatase Pyst1 catalytic domain and implications for regulated activation. Nature structural biology 138 10048930
2018 PKN2 in colon cancer cells inhibits M2 phenotype polarization of tumor-associated macrophages via regulating DUSP6-Erk1/2 pathway. Molecular cancer 118 29368606
2005 Extracellular signal-regulated kinases phosphorylate mitogen-activated protein kinase phosphatase 3/DUSP6 at serines 159 and 197, two sites critical for its proteasomal degradation. Molecular and cellular biology 116 15632084
2021 Paralog knockout profiling identifies DUSP4 and DUSP6 as a digenic dependence in MAPK pathway-driven cancers. Nature genetics 115 34857952
2005 Abrogation of DUSP6 by hypermethylation in human pancreatic cancer. Journal of human genetics 113 15824892
2000 Nitric oxide down-regulates MKP-3 mRNA levels: involvement in endothelial cell protection from apoptosis. The Journal of biological chemistry 112 10846176
1998 Isolation of the human genes encoding the pyst1 and Pyst2 phosphatases: characterisation of Pyst2 as a cytosolic dual-specificity MAP kinase phosphatase and its catalytic activation by both MAP and SAP kinases. Journal of cell science 109 9788880
2018 Dual-specificity phosphatase 6 (DUSP6): a review of its molecular characteristics and clinical relevance in cancer. Cancer biology & medicine 106 29545965
2005 Distinct progression pathways involving the dysfunction of DUSP6/MKP-3 in pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms of the pancreas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 103 15832194
2009 Down-regulation of DUSP6 expression in lung cancer: its mechanism and potential role in carcinogenesis. The American journal of pathology 98 19608870
2011 Dual-specificity phosphatase DUSP6 has tumor-promoting properties in human glioblastomas. Oncogene 87 21499306
2007 DUSP6/MKP-3 inactivates ERK1/2 but fails to bind and inactivate ERK5. Cellular signalling 76 18280112
2021 Identification of a gut microbiota member that ameliorates DSS-induced colitis in intestinal barrier enhanced Dusp6-deficient mice. Cell reports 75 34818535
2017 Pharmacological inhibition of DUSP6 suppresses gastric cancer growth and metastasis and overcomes cisplatin resistance. Cancer letters 74 29050982
2017 Enhancement of macrophage inflammatory responses by CCL2 is correlated with increased miR-9 expression and downregulation of the ERK1/2 phosphatase Dusp6. Cellular immunology 73 28242024
2011 Tumor suppressor dual-specificity phosphatase 6 (DUSP6) impairs cell invasion and epithelial-mesenchymal transition (EMT)-associated phenotype. International journal of cancer 70 21387288
2014 Global MEF2 target gene analysis in cardiac and skeletal muscle reveals novel regulation of DUSP6 by p38MAPK-MEF2 signaling. Nucleic acids research 69 25217591
1998 Genomic analysis of DUSP6, a dual specificity MAP kinase phosphatase, in pancreatic cancer. Cytogenetics and cell genetics 69 9858808
2020 DUSP6 SUMOylation protects cells from oxidative damage via direct regulation of Drp1 dephosphorylation. Science advances 67 32232156
2008 Post-translational regulation of the ERK phosphatase DUSP6/MKP3 by the mTOR pathway. Oncogene 66 18223677
2019 Targeted Inhibition of the Dual Specificity Phosphatases DUSP1 and DUSP6 Suppress MPNST Growth via JNK. Clinical cancer research : an official journal of the American Association for Cancer Research 65 30936125
2011 Post-transcriptional regulation of the DUSP6/MKP-3 phosphatase by MEK/ERK signaling and hypoxia. Journal of cellular physiology 64 20665674
2018 Dusp6 attenuates Ras/MAPK signaling to limit zebrafish heart regeneration. Development (Cambridge, England) 59 29444893
2017 DUSP5 and DUSP6, two ERK specific phosphatases, are markers of a higher MAPK signaling activation in BRAF mutated thyroid cancers. PloS one 56 28910386
2014 Mitogen-activated protein kinase phosphatase 3 (MKP-3)-deficient mice are resistant to diet-induced obesity. Diabetes 56 24722245
2019 Long non-coding RNA TUG1 promotes airway remodelling by suppressing the miR-145-5p/DUSP6 axis in cigarette smoke-induced COPD. Journal of cellular and molecular medicine 55 31557398
2018 DUSP6 mediates T cell receptor-engaged glycolysis and restrains TFH cell differentiation. Proceedings of the National Academy of Sciences of the United States of America 50 30087184
2013 DUSP6/MKP3 is overexpressed in papillary and poorly differentiated thyroid carcinoma and contributes to neoplastic properties of thyroid cancer cells. Endocrine-related cancer 50 23132790
2002 Expression of the ERK-specific MAP kinase phosphatase PYST1/MKP3 in mouse embryos during morphogenesis and early organogenesis. Mechanisms of development 50 11960712
2022 DUSP6 mediates resistance to JAK2 inhibition and drives leukemic progression. Nature cancer 46 36581736
2013 A missense mutation in DUSP6 is associated with Class III malocclusion. Journal of dental research 45 23965468
2008 Feedback regulation of DUSP6 transcription responding to MAPK1 via ETS2 in human cells. Biochemical and biophysical research communications 44 18848526
2021 Hydrogen sulfide exposure induces pyroptosis in the trachea of broilers via the regulatory effect of circRNA-17828/miR-6631-5p/DUSP6 crosstalk on ROS production. Journal of hazardous materials 43 34098264
2015 Hepatitis C virus-induced reduction in miR-181a impairs CD4(+) T-cell responses through overexpression of DUSP6. Hepatology (Baltimore, Md.) 43 25477247
2010 p-MAPK1/3 and DUSP6 regulate epididymal cell proliferation and survival in a region-specific manner in mice. Biology of reproduction 43 20650883
2012 Expression of protein-tyrosine phosphatases in Acute Myeloid Leukemia cells: FLT3 ITD sustains high levels of DUSP6 expression. Cell communication and signaling : CCS 41 22784513
2013 A Common Docking Domain in Progesterone Receptor-B links DUSP6 and CK2 signaling to proliferative transcriptional programs in breast cancer cells. Nucleic acids research 40 23921636
2022 Dusp6 deficiency attenuates neutrophil-mediated cardiac damage in the acute inflammatory phase of myocardial infarction. Nature communications 37 36335128
2014 TSH signaling overcomes B-RafV600E-induced senescence in papillary thyroid carcinogenesis through regulation of DUSP6. Neoplasia (New York, N.Y.) 37 25499223
2012 Ischemia/reperfusion-induced MKP-3 impairs endothelial NO formation via inactivation of ERK1/2 pathway. PloS one 36 22848708
2011 Dual-specific phosphatase-6 (Dusp6) and ERK mediate AMPA receptor-induced oligodendrocyte death. The Journal of biological chemistry 36 21300799
2008 Expression of ERK signaling inhibitors Dusp6, Dusp7, and Dusp9 during mouse ear development. Developmental dynamics : an official publication of the American Association of Anatomists 33 18058922
2013 DUSP6 regulates drug sensitivity by modulating DNA damage response. British journal of cancer 31 23839489
2019 Tripartite motif-containing protein 7 regulates hepatocellular carcinoma cell proliferation via the DUSP6/p38 pathway. Biochemical and biophysical research communications 30 30850165
2021 Loss of FBXO31-mediated degradation of DUSP6 dysregulates ERK and PI3K-AKT signaling and promotes prostate tumorigenesis. Cell reports 29 34686346
2014 FOXO1-dependent up-regulation of MAP kinase phosphatase 3 (MKP-3) mediates glucocorticoid-induced hepatic lipid accumulation in mice. Molecular and cellular endocrinology 29 24946098
2023 N6-methyadenosine modified SUV39H2 regulates homologous recombination through epigenetic repression of DUSP6 in gastric cancer. Cancer letters 27 36806557
2021 DUSP6 expression is associated with osteoporosis through the regulation of osteoclast differentiation via ERK2/Smad2 signaling. Cell death & disease 27 34475393
2020 Overexpression of DUSP6 enhances chemotherapy-resistance of ovarian epithelial cancer by regulating the ERK signaling pathway. Journal of Cancer 27 32231719
2020 CIC Is a Mediator of the ERK1/2-DUSP6 Negative Feedback Loop. iScience 27 33103082
2019 DUSP6 Inhibitor (E/Z)-BCI Hydrochloride Attenuates Lipopolysaccharide-Induced Inflammatory Responses in Murine Macrophage Cells via Activating the Nrf2 Signaling Axis and Inhibiting the NF-κB Pathway. Inflammation 27 30506106
2018 Dual specificity phosphatase DUSP6 promotes endothelial inflammation through inducible expression of ICAM-1. The FEBS journal 26 29493888
2021 NKX2-1 controls lung cancer progression by inducing DUSP6 to dampen ERK activity. Oncogene 25 34689179
2019 Role of Dusp6 Phosphatase as a Tumor Suppressor in Non-Small Cell Lung Cancer. International journal of molecular sciences 25 31027181
2013 Lef1 regulates Dusp6 to influence neuromast formation and spacing in the zebrafish posterior lateral line primordium. Development (Cambridge, England) 25 23637337
2011 The genetic association of DUSP6 with bipolar disorder and its effect on ERK activity. Progress in neuro-psychopharmacology & biological psychiatry 25 22155192
2000 Association study on the DUSP6 gene, an affective disorder candidate gene on 12q23, performed by using fluorescence resonance energy transfer-based melting curve analysis on the LightCycler. Molecular psychiatry 25 11035444
1997 Chromosomal localization of three human dual specificity phosphatase genes (DUSP4, DUSP6, and DUSP7). Genomics 25 9205128
2020 MicroRNA-211 Modulates the DUSP6-ERK5 Signaling Axis to Promote BRAFV600E-Driven Melanoma Growth In Vivo and BRAF/MEK Inhibitor Resistance. The Journal of investigative dermatology 24 32888955
2018 ATM Dependent DUSP6 Modulation of p53 Involved in Synergistic Targeting of MAPK and p53 Pathways with Trametinib and MDM2 Inhibitors in Cutaneous Melanoma. Cancers 23 30577494
2015 MicroRNA-145 inhibits human papillary cancer TPC1 cell proliferation by targeting DUSP6. International journal of clinical and experimental medicine 23 26309510
2012 MEK/ERK pathway mediates insulin-promoted degradation of MKP-3 protein in liver cells. Molecular and cellular endocrinology 23 22521266
2021 Upregulation of DUSP6 impairs infectious bronchitis virus replication by negatively regulating ERK pathway and promoting apoptosis. Veterinary research 22 33431056
2019 Inhibition of DUSP6 sensitizes ovarian cancer cells to chemotherapeutic agents via regulation of ERK signaling response genes. Oncotarget 22 31164954
2019 Dusp6 inhibits epithelial-mesenchymal transition in endometrial adenocarcinoma via ERK signaling pathway. Radiology and oncology 22 31553703
2022 Cynarin attenuates LPS-induced endothelial inflammation via upregulation of the negative regulator MKP-3. Animal cells and systems 21 35784390
2022 Insights into the role of P2X7R/DUSP6/ERK1/2 and SIRT2/MDM2 signaling in the nephroprotective effect of berberine against cisplatin-induced renal fibrosis in rats. Life sciences 21 36208663
2013 DUSP6, a tumor suppressor, is involved in differentiation and apoptosis in esophageal squamous cell carcinoma. Oncology letters 21 24260056
2012 Mapping MKP-3/FOXO1 interaction and evaluating the effect on gluconeogenesis. PloS one 21 22848439
2021 Short-Chain Fatty Acid Decreases the Expression of CEBPB to Inhibit miR-145-Mediated DUSP6 and Thus Further Suppresses Intestinal Inflammation. Inflammation 20 34792688
2020 DUSP6 protects murine podocytes from high glucose‑induced inflammation and apoptosis. Molecular medicine reports 20 32705203
2010 DUSP5 and DUSP6 modulate corneal epithelial cell proliferation. Molecular vision 20 20806045
2019 Nuclear-Biased DUSP6 Expression is Associated with Cancer Spreading Including Brain Metastasis in Triple-Negative Breast Cancer. International journal of molecular sciences 19 31238530
2018 The testosterone metabolite 3α-androstanediol inhibits oxidative stress-induced ERK phosphorylation and neurotoxicity in SH-SY5Y cells through an MKP3/DUSP6-dependent mechanism. Neuroscience letters 19 30552945
2015 Silencing of DUSP6 gene by RNAi-mediation inhibits proliferation and growth in MDA-MB-231 breast cancer cells: an in vitro study. International journal of clinical and experimental medicine 19 26379838
2012 Increased levels of DUSP6 phosphatase stimulate tumourigenesis in a molecularly distinct melanoma subtype. Pigment cell & melanoma research 19 22171919
2017 Systematic screening of isogenic cancer cells identifies DUSP6 as context-specific synthetic lethal target in melanoma. Oncotarget 17 28423600
2021 TRIM65 Promotes Invasion of Endometrial Stromal Cells by Activating ERK1/2/C-myc Signaling via Ubiquitination of DUSP6. The Journal of clinical endocrinology and metabolism 16 33146694
2020 Mice lacking DUSP6/8 have enhanced ERK1/2 activity and resistance to diet-induced obesity. Biochemical and biophysical research communications 16 32917360
2019 Dusp6 is a genetic modifier of growth through enhanced ERK activity. Human molecular genetics 16 30289454
2013 Dual-specificity phosphatase 6 (Dusp6), a negative regulator of FGF2/ERK1/2 signaling, enhances 17β-estradiol-induced cell growth in endometrial adenocarcinoma cell. Molecular and cellular endocrinology 16 23419500
2013 Spinal mitogen-activated protein kinase phosphatase-3 (MKP-3) is necessary for the normal resolution of mechanical allodynia in a mouse model of acute postoperative pain. The Journal of neuroscience : the official journal of the Society for Neuroscience 16 24155322
2022 A DUSP6 inhibitor suppresses inflammatory cardiac remodeling and improves heart function after myocardial infarction. Disease models & mechanisms 15 36478044
2014 Nε-carboxymethyllysine-mediated endoplasmic reticulum stress promotes endothelial cell injury through Nox4/MKP-3 interaction. Free radical biology & medicine 15 25014566
2020 Dual-specificity phosphatase (DUSP6) in human glioblastoma: epithelial-to-mesenchymal transition (EMT) involvement. BMC research notes 14 32771050
2024 DUSP6 inhibition overcomes neuregulin/HER3-driven therapy tolerance in HER2+ breast cancer. EMBO molecular medicine 13 38886591
2022 LncRNA TCONS_00145741 Knockdown Prevents Thrombin-Induced M1 Differentiation of Microglia in Intracerebral Hemorrhage by Enhancing the Interaction Between DUSP6 and JNK. Frontiers in cell and developmental biology 13 35127692
2012 Caspase-3 cleavage of DUSP6/MKP3 at the interdomain region generates active MKP3 fragments that regulate ERK1/2 subcellular localization and function. Journal of molecular biology 13 22504224
2021 DUSP6 regulates radiosensitivity in glioblastoma by modulating the recruitment of phosphorylated DNAPKcs at DNA double-strand breaks. Journal of cell science 12 34792128