Affinage

DUSP4

Dual specificity protein phosphatase 4 · UniProt Q13115

Length
394 aa
Mass
43.0 kDa
Annotated
2026-06-09
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DUSP4 (MKP-2/HVH2/TYP) is a nuclear dual-specificity phosphatase that serves as a negative-feedback brake on MAPK signaling, dephosphorylating both the phosphothreonine and phosphotyrosine of activated ERK1/2 and JNK—but not p38—to terminate kinase activity and restrain transcriptional output (PMID:7535768, PMID:8545112, PMID:8626452). Its catalytic output is governed by an autoinhibitory C-terminus, removal of which markedly increases phosphatase activity toward MAPK substrates (PMID:12083364), and its abundance is set by an ERK-driven feedback loop in which ERK phosphorylates C-terminal serine residues (S386/S391 and additional MEK-dependent sites) to protect the protein from proteasomal degradation (PMID:21084841, PMID:25204653, PMID:22430215). DUSP4 is transcriptionally induced downstream of diverse stimuli—oncogenic KRAS/BRAF via MEK (PMID:22430215), AMPK via EGR1 (PMID:16849326), PDGF via ERK/STAT3/p53 (PMID:31526568), and through STAT3/YY1/CTCF promoter elements (PMID:34254709)—and acts as a tumor suppressor whose silencing by promoter hypermethylation, genomic 8p loss, or chromatin remodeling (ARID1A loss, G9a) hyperactivates ERK and JNK to drive proliferation, cancer stem-cell expansion, invasion, and chemoresistance across breast, lymphoma, pancreatic, and other cancers (PMID:20124482, PMID:22683778, PMID:23966295, PMID:25847947, PMID:30475228, PMID:38071325). Beyond canonical MAPK kinases, DUSP4 has substrate and complex roles extending its reach: it forms a GR–JNK1 complex to dephosphorylate JNK1 and control glucocorticoid receptor nuclear translocation (PMID:28283554), binds and dephosphorylates HSP90β at T214/Y216 to activate its ATPase and stabilize JAK-STAT3 signaling (PMID:37141098), dephosphorylates ALDOB to restrict G6PD/ROS metabolism (PMID:38843658), and participates in a TBK1–ERK1/2–IRF3 complex governing type I interferon production (PMID:38383887). Genetic loss-of-function in mice and zebrafish establishes non-redundant roles in cell-cycle progression and apoptosis (PMID:21317287), CD4+ T-cell proliferation via STAT5/IL-2 (PMID:22101742), endoderm specification (PMID:18719100), cardiac and podocyte protection through p38/JNK control (PMID:26184564, PMID:30862678), and metabolic regulation of obesity and hepatic steatosis (PMID:35745205).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1995 High

    Established DUSP4 as a catalytically active dual-specificity phosphatase that directly inactivates ERK MAPKs and acts in the nucleus, answering what biochemical activity the gene encodes.

    Evidence In vitro phosphatase assays with recombinant/purified protein on ERK1/2 and ERK2/JNK, immunofluorescence localization, and SRE reporter assays in NIH3T3 and COS cells

    PMID:7535768 PMID:8545112

    Open questions at the time
    • In vivo substrate hierarchy not yet resolved
    • Regulation of phosphatase activity unaddressed
  2. 1996 High

    Defined the in vivo substrate specificity of DUSP4 as ERK and JNK but not p38, distinguishing it from related MKPs and clarifying which pathways it feeds back upon.

    Evidence In vivo co-expression substrate specificity assays in T cells with a hyperactive ERK2 (sevenmaker) allele

    PMID:8626452

    Open questions at the time
    • Does not explain p38 effects seen later in disease models
    • Cellular context-dependence of specificity unresolved
  3. 2002 High

    Showed that the C-terminal domain autoinhibits catalytic activity, revealing an intrinsic regulatory mechanism controlling phosphatase output.

    Evidence C-terminal deletion mutagenesis with in vivo and in vitro phosphatase activity measurements

    PMID:12083364

    Open questions at the time
    • Structural basis of autoinhibition not defined
    • Physiological trigger relieving inhibition unknown at this point
  4. 2006 High

    Connected DUSP4 to metabolic transcriptional control, establishing an AMPK→EGR1→DUSP4→p38 axis repressing gluconeogenic gene expression.

    Evidence ChIP, reporter assays, siRNA, and constitutively active p38 rescue in hepatocytes

    PMID:16849326

    Open questions at the time
    • Whether DUSP4 acts on p38 directly in this setting not enzymatically shown
    • In vivo metabolic relevance untested here
  5. 2008 Medium

    Demonstrated an essential developmental role, showing dusp4 is required for endoderm specification, extending its function beyond feedback regulation.

    Evidence Morpholino knockdown in zebrafish with sox17 marker analysis and transplantation

    PMID:18719100

    Open questions at the time
    • Morpholino off-target effects not excluded
    • Molecular substrate driving endoderm phenotype unidentified
  6. 2010 High

    Resolved how DUSP4 stability is controlled, identifying ERK-mediated C-terminal serine phosphorylation as a stabilizing feedback signal and mapping MEK-dependent phospho-sites that spatially confine ERK activity in oncogene-driven cells.

    Evidence Phospho-site mutagenesis, cycloheximide chase, proteasome and ERK inhibitors, and oncogenic KRAS/BRAF expression with ERK spatial mapping

    PMID:21084841 PMID:22430215

    Open questions at the time
    • Kinase responsible for stabilization vs. canonical ERK feedback not fully separated
    • E3 ligase mediating degradation unidentified
  7. 2011 High

    Genetic loss-of-function in mice established non-redundant roles in cell-cycle progression, apoptosis, and CD4+ T-cell proliferation control.

    Evidence DUSP4 knockout MEFs and mice with adenoviral rescue, cell-cycle analysis, and STAT5 phosphorylation readouts

    PMID:21317287 PMID:22101742

    Open questions at the time
    • Direct substrate for STAT5 regulation in T cells unclear
    • Tissue-specific requirements not dissected
  8. 2012 High

    Defined DUSP4 as an epigenetically silenced tumor suppressor whose loss activates Ras-ERK and modulates chemosensitivity in basal-like breast cancer.

    Evidence Gain/loss-of-function in breast cancer cell lines, promoter methylation analysis, MEK-inhibitor combination, and xenografts

    PMID:20124482 PMID:22683778

    Open questions at the time
    • Cause of selective promoter methylation unknown
    • Whether ERK is the sole driver of chemoresistance untested
  9. 2013 High

    Extended the tumor-suppressor mechanism to dual MEK/ERK and JNK control of cancer stem-cell populations and inflammatory cytokine output via ETS-1 and c-JUN.

    Evidence Knockdown/overexpression in BLBC lines, mammosphere and flow-cytometry assays, MEK-inhibitor rescue, and xenografts

    PMID:23966295

    Open questions at the time
    • Relative contribution of ERK vs JNK arms not quantified
    • Direct transcription-factor dephosphorylation not shown
  10. 2014 High

    Confirmed C-terminal serine phosphorylation as the stability determinant in macrophages and broadened DUSP4 function into neuronal differentiation and inflammatory regulation.

    Evidence Phospho-site mutagenesis with half-life and ubiquitination assays in macrophages; knockdown/rescue in ES-derived neurons; G9a-inhibition autophagy studies

    PMID:25027955 PMID:25204653 PMID:25397900

    Open questions at the time
    • Degradation pathway independent of ubiquitination not mechanistically explained
    • Calcium-pathway substrates not identified
  11. 2015 High

    Demonstrated catalytic JNK dephosphorylation drives apoptosis in lymphoma and uncovered a novel GR–JNK1–DUSP4 complex controlling glucocorticoid receptor translocation, expanding the substrate repertoire beyond free MAPKs.

    Evidence Phosphatase-dead mutant rescue and methylation analysis in DLBCL; co-immunoprecipitation, IP-phosphatase activity assay, and GR-Ser226 readouts

    PMID:25847947 PMID:28283554

    Open questions at the time
    • Stoichiometry and assembly of the GR-JNK1 complex unresolved
    • Direct GR dephosphorylation vs JNK-mediated indirect effect not fully separated
  12. 2016 Medium

    Established DUSP4 loss at 8p as a driver of invasive progression and showed broad phosphoprotein-level suppression of ERK, p38, JNK, RB, and NF-κB upon DUSP4 induction.

    Evidence Re-expression in pancreatic and TNBC lines, invasion/anoikis assays, phosphoprotein microarray, and orthotopic xenografts

    PMID:26941286 PMID:27393618

    Open questions at the time
    • Direct vs indirect targets among the 172 phosphoproteins not distinguished
    • Mechanism of cell-cycle arrest not assigned to a specific substrate
  13. 2018 High

    Genetic interaction studies revealed cooperative tumor suppression with Dok2 in lung tumorigenesis, reinforcing DUSP4 as a MAPK-restraining suppressor.

    Evidence Compound heterozygous Dok2/Dusp4 mouse knockout with tumor monitoring and restoration experiments

    PMID:30475228

    Open questions at the time
    • Molecular basis of Dok2-DUSP4 cooperation unresolved
    • Whether the interaction is physical or pathway-level unknown
  14. 2019 High

    Defined DUSP4 as a feedback tuner across diverse physiological circuits—circadian VIP/ERK signaling in the SCN, diabetic podocyte protection via p38/JNK/Nox4, and PDGF-driven ERK/STAT3/p53 induction.

    Evidence Ex vivo SCN slice culture; DUSP4-/- diabetic mice and podocyte overexpression with PKC-δ inhibition; PDGF stimulation with regulator knockdowns

    PMID:30710088 PMID:30862678 PMID:31526568

    Open questions at the time
    • Direct p38/JNK dephosphorylation in podocytes not enzymatically demonstrated
    • Tissue-specific upstream inducers incompletely mapped
  15. 2022 High

    Linked chromatin regulation (ARID1A, histone acetylation) to DUSP4 silencing and uncovered context-dependent, non-canonical ERK regulation in melanoma where DUSP4 loss acts through DUSP6.

    Evidence ChIP-seq/RNA-seq with ARID1A loss and ectopic DUSP4 rescue; DUSP4/DUSP6 double-knockout epistasis and kinase translocation reporters in melanoma; metabolic KO mouse phenotyping

    PMID:35189148 PMID:35580987 PMID:35745205 PMID:38071325

    Open questions at the time
    • Reconciliation of direct ERK-phosphatase model with DUSP6-dependent paradoxical effect unresolved
    • Mechanism of DUSP6 post-transcriptional upregulation unknown
  16. 2024 High

    Expanded the substrate landscape to non-MAPK proteins, showing DUSP4 binds and dephosphorylates HSP90β to activate JAK-STAT3, dephosphorylates ALDOB to restrict G6PD/ROS metabolism, and scaffolds a TBK1-ERK1/2-IRF3 complex governing type I interferon and antimicrobial defense.

    Evidence Co-IP/pulldown with phospho-site mapping and ATPase assays for HSP90β; IP-MS and enzyme assays for ALDOB; reciprocal Co-IP and DUSP4-/- infection models for the TBK1-IRF3 complex

    PMID:37141098 PMID:38383887 PMID:38843658

    Open questions at the time
    • Whether these non-MAPK activities share a common recognition motif unknown
    • Structural basis of substrate selection unresolved
  17. 2025 Medium

    Connected DUSP4 to cancer metabolism and immune modulation through new substrates, dephosphorylating PGK1-associated ERK to alter glycolysis/ROS and CDK7 to drive CXCL16 expression and CD8+ T-cell infiltration while suppressing ferroptosis.

    Evidence Phosphoproteomics, Co-IP, mitochondrial fractionation, ferroptosis and metabolic assays, and in vivo tumor models in ovarian and MSI colorectal cancers

    PMID:40082940 PMID:40847010

    Open questions at the time
    • Direct CDK7 dephosphorylation requires reconstitution
    • Substrate findings from single labs await independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how DUSP4 achieves substrate selection across its expanding set of canonical (ERK/JNK) and non-canonical (HSP90β, ALDOB, CDK7, PGK1, TBK1-IRF3) targets and how this selectivity is partitioned between tumor-suppressive and context-dependent oncogenic outcomes.
  • No structural model defines substrate recognition
  • Whether non-MAPK substrates are dephosphorylated by the same catalytic mechanism is unestablished
  • Determinants distinguishing tumor-suppressor vs DUSP6-mediated paradoxical roles unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016787 hydrolase activity 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 2 R-HSA-168256 Immune System 2
Partners
ALDOBCDK7ERK1/2GRHSP90B1IRF3JNK1TBK1
Complex memberships
GR-JNK1-DUSP4 complexTBK1-ERK1/2-IRF3 complex

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 HVH2 (DUSP4) is a dual-specificity phosphatase that selectively dephosphorylates both phosphothreonine and phosphotyrosine residues of activated ERK1 and ERK2 in vitro, and localizes to the cell nucleus. Transfection into NIH3T3 cells inhibited v-src and MEK-induced transcriptional activation of SRE-containing promoters. In vitro phosphatase assay with recombinant protein, immunofluorescence of epitope-tagged protein, transfection/reporter assay The Journal of biological chemistry High 7535768
1995 TYP1 (DUSP4) encodes a nuclear dual-specificity phosphatase that inactivates both ERK2 and p54 JNK. Purified TYP1 protein efficiently dephosphorylates both phosphothreonine and phosphotyrosine of recombinant ERK2 in vitro. In COS cells, TYP1 protein is stabilized by EGF treatment. In vitro phosphatase assay with purified protein, transfection in COS-1 cells, northern analysis for expression kinetics Oncogene High 8545112
1996 MKP-2 (DUSP4) has a unique in vivo substrate specificity toward ERK and JNK (but not p38), distinguishing it from PAC1 (ERK/p38) and MKP-1 (ERK/p38/JNK). A hyperactive ERK2 allele (D319N, sevenmaker) showed significantly reduced sensitivity to MKP-2 dephosphorylation in vivo. In vivo substrate specificity assay in T cells using phorbol ester stimulation, co-expression of phosphatases with MAP kinase substrates The Journal of biological chemistry High 8626452
1997 DUSP4 (MKP-2) gene maps to chromosomal location 8p11-p12 by fluorescence in situ hybridization and radiation hybrid mapping. Fluorescence in situ hybridization (FISH), radiation hybrid mapping Genomics Medium 9205128
2002 The C-terminal domain of MKP-2 (DUSP4) exerts an inhibitory effect on its phosphatase activity. C-terminal truncation of MKP-2 substantially increased phosphatase activity toward MAPK substrates both in vivo and in vitro without changing substrate affinity or substrate-mediated catalytic activation. C-terminal deletion mutagenesis, in vivo and in vitro phosphatase activity assays Molecular and cellular biochemistry High 12083364
2003 I1-imidazoline receptor stimulation with moxonidine induces MKP-2 (DUSP4) protein levels approximately 3-fold in PC12 cells and reverses NGF-induced ERK activation, effects blocked by the I1-antagonist efaroxan or by D609 (phosphatidylcholine-selective PLC inhibitor), placing DUSP4 induction downstream of I1-receptor/phospholipase C signaling. Western blot for MKP-2 protein, pharmacological inhibitors, ERK activation assay in PC12 cells Brain research Medium 12865160
2006 AMPK activation (by AICAR) induces DUSP4 expression in hepatocytes via transcriptional induction of EGR1, which directly binds the DUSP4 promoter. DUSP4 in turn inhibits promoter activity and expression of gluconeogenic genes PEPCK and Glucose-6-phosphatase. Constitutively active p38 rescued DUSP4-mediated repression of PEPCK. siRNA depletion of EGR1 or DUSP4 partially abrogated AICAR-mediated inhibition of PEPCK and glucose production. Reporter gene assays, real-time PCR, siRNA knockdown, ChIP (EGR1 binding to DUSP4 promoter), constitutively active p38 rescue The Journal of biological chemistry High 16849326
2008 dusp4 is essential for early zebrafish endoderm specification; morpholino-mediated knockdown caused necrosis of head tissues and a specific loss of sox17 expression (but not other endoderm markers), indicating a required role in foregut and pancreatic endoderm formation. Antisense morpholino oligonucleotide knockdown in zebrafish, marker analysis (in situ hybridization for sox17), transplantation assays Proceedings of the National Academy of Sciences of the United States of America Medium 18719100
2010 Oncogenic KRAS(G12V) and BRAF(V600E) induce rapid nuclear accumulation of DUSP4 (in an MEK-dependent manner), which dephosphorylates and restricts ERK phosphorylation specifically to the cytoplasm in intestinal epithelial cells. MEK-dependent phosphorylation of DUSP4 at T361, T363, S390, and S395 residues stabilizes the protein. In human colorectal cancer cells, ERK activity was similarly confined to the cytoplasm and treatment with pervanadate reactivated nuclear ERK. Expression of oncogenic KRAS/BRAF in IECs, immunofluorescence for ERK phosphorylation, MEK inhibitor treatment, phospho-site mapping, pervanadate treatment in CRC cells Oncogene High 22430215
2010 MKP-2 (DUSP4) is phosphorylated by ERK at Ser386 and Ser391 in its C-terminus, and this phosphorylation stabilizes MKP-2 protein by protecting it from proteasomal degradation. Blockade of ERK activation enhanced proteasomal degradation of MKP-2, and phosphorylation had no effect on MKP-2 phosphatase activity. Site-directed mutagenesis of phospho-sites (S386, S391), ERK inhibitor treatment, proteasome inhibitor assay, Western blot for protein stability Cell cycle (Georgetown, Tex.) High 21084841
2010 DUSP4/MKP-2 promoter CpG island hypermethylation in gliomas reduces MKP-2 mRNA and protein expression. Treatment with 5-aza-2'-deoxycytidine (demethylating agent) increased MKP-2 mRNA, and exogenous MKP-2 overexpression inhibited glioblastoma cell growth. Differential methylation hybridization, 5-aza-2'-deoxycytidine demethylation, overexpression growth assay in glioblastoma cells Cancer research Medium 20124482
2011 DUSP4/MKP-2 knockout MEFs show enhanced PDGF-induced sustained ERK phosphorylation and moderately increased JNK phosphorylation, reduced cellular proliferation (with block at G2/M associated with cyclin B accumulation and enhanced cdc2 phosphorylation), and enhanced anisomycin-induced apoptosis (increased caspase-3 cleavage and γH2AX). Adenoviral re-expression of MKP-2 reversed both proliferation defects and JNK-associated apoptosis. MKP-2 knockout MEFs from deletion mouse model, adenoviral MKP-2 rescue, cell cycle analysis, Western blot for cyclin B/cdc2/caspase-3/γH2AX The Journal of biological chemistry High 21317287
2011 DUSP4 deficiency in mice results in hyperproliferation of activated CD4+ T cells (but not CD8+ T cells) due to enhanced CD25 expression and increased IL-2 signaling through elevated STAT5 phosphorylation, revealing a role for DUSP4 in suppressing CD4+ T-cell proliferation via STAT5/IL-2 pathway regulation. DUSP4 knockout mouse, T-cell proliferation assays, STAT5 phosphorylation by Western blot, immunization recall response European journal of immunology High 22101742
2012 DUSP4 is an ERK phosphatase whose loss in basal-like breast cancer (BLBC) correlates with DUSP4 promoter methylation and activates the Ras-ERK pathway. DUSP4 overexpression increased chemotherapy-induced apoptosis in BLBC cells, while DUSP4 depletion dampened the chemotherapy response. MEK inhibition synergized with docetaxel in BLBC xenografts. DUSP4 overexpression and siRNA knockdown in breast cancer cell lines, xenograft model, MEK inhibitor combination, digital transcript counting of post-NAC tumors Nature medicine High 22683778
2012 MKP-2 (DUSP4) knockdown in macrophages attenuated the proinflammatory cytokine production and neutrophil infiltration in a murine LPS-induced acute lung injury model. MKP-2 knockdown was associated with increased ERK phosphorylation and induction of MKP-1, suggesting a regulatory interplay between these DUSPs. MKP-2 null mice (MKP-2−/−), MKP-2 knockdown in macrophage cell line, intratracheal LPS model, cytokine measurement, neutrophil counting American journal of physiology. Lung cellular and molecular physiology Medium 22683570
2013 DUSP4 loss in basal-like breast cancer activates both MEK/ERK and JNK pathways, increasing mammosphere formation, CD44+/CD24- cancer stem cell-like populations, and IL-6/IL-8 expression through downstream ETS-1 and c-JUN transcription factors. Enforced DUSP4 expression reduced cancer stem cell populations in a MEK-dependent manner. DUSP4 knockdown/overexpression in BLBC cell lines, mammosphere assay, flow cytometry for CD44+/CD24−, cytokine measurement, MEK inhibitor rescue, xenograft tumor formation Cancer research High 23966295
2013 DUSP4 is induced by hCG/LH in MA-10 Leydig cells via cAMP/PKA signaling, and MKP-2 downregulation by shRNA elevated phosphorylated ERK1/2 after 8Br-cAMP stimulation and increased CYP11A1 (P450scc) promoter activity and mRNA levels, demonstrating that MKP-2 modulates the late phase of cAMP-induced ERK1/2 activity and consequently CYP11A1 expression. shRNA knockdown, promoter-reporter assay, hCG/8Br-cAMP stimulation, phospho-ERK1/2 Western blot, mRNA quantification Endocrinology Medium 23471219
2014 Inhibition of the histone methyltransferase G9a induces DUSP4-dependent ERK inactivation and autophagic cell death in head and neck squamous cell carcinoma cells, identifying DUSP4 as a downstream mediator linking G9a inhibition to autophagy. G9a genetic/pharmacological inhibition, Affymetrix microarray for target identification, immunoblot, flow cytometry, fluorescent/electron microscopy, xenograft model Molecular cancer Medium 25027955
2014 DUSP4 regulates neuronal differentiation and calcium homeostasis by modulating ERK1/2 phosphorylation. DUSP4 knockdown reduced neurite outgrowth and neuronal marker expression (rescued by DUSP4 reintroduction), enhanced ERK activation during differentiation, and altered calcium signaling by regulating CaMKI phosphorylation and Cav1.2 expression and plasma membrane localization. DUSP4 knockdown/reintroduction in embryonic stem cell-derived neurons, neurite outgrowth assay, Western blot for ERK/CaMKI, Cav1.2 localization by imaging Stem cells and development Medium 25397900
2014 MKP-2 (DUSP4) stability in macrophages is regulated by ERK-mediated phosphorylation of two C-terminal serine residues. Mutation of these serines to alanine decreased MKP-2 half-life, while aspartate substitution dramatically increased it. C-terminal truncation also increased stability. Enhanced stability was not associated with decreased ubiquitination; degradation required proteasome activity. Site-directed mutagenesis of C-terminal serines, half-life measurement by cycloheximide chase, proteasome inhibitor, ubiquitination assays, ERK pathway inhibitor The Journal of biological chemistry High 25204653
2015 Ectopic expression of wild-type DUSP4, but not a phosphatase-deficient mutant, dephosphorylates JNK and induces apoptosis in diffuse large B cell lymphoma (DLBCL) cells. DUSP4 loss is caused by CpG island promoter hypermethylation and genomic deletion, and DLBCL cells depend on JNK signaling for survival. Ectopic expression of WT vs. phosphatase-dead DUSP4 mutant, JNK phosphorylation assay, apoptosis assay, genome-wide DNA methylation analysis The Journal of experimental medicine High 25847947
2015 DUSP4 modulates p38 phosphorylation in endothelial cells and heart. DUSP4 is degraded by hypoxia/reoxygenation (H/R) and its loss correlates with p38 hyperphosphorylation and apoptosis. DUSP4-/- hearts showed larger infarcts with overactivated p38 after ischemia/reperfusion. p38 inhibition rescued both WT and DUSP4-/- cardiac function. DUSP4 knockdown (siRNA), DUSP4-/- mouse Langendorff-perfused heart model, TUNEL assay, Western blot for p38/caspase-3, p38 inhibitor (SB203580) Free radical biology & medicine High 26184564
2015 Increased DUSP4 expression in CD4+ T cells from idiopathic CD4 lymphopenia (ICL) patients suppresses TCR-induced ERK activation and downregulates CD27 and CD40L. siRNA normalization of DUSP4 expression in ICL cells restored ERK activation and costimulatory molecule expression. Repeated TCR stimulation in control T cells induced DUSP4 overexpression and TCR signal dampening, both curtailed by DUSP4 silencing. siRNA knockdown in primary human T cells from ICL patients, TCR stimulation, ERK phosphorylation assay, flow cytometry for surface markers Blood Medium 25733583
2016 Restoration of DUSP4 expression in pancreatic cancer cells suppressed invasiveness and anoikis resistance via ERK inactivation, and MEK inhibition was effective in an orthotopic xenograft model. DUSP4 genomic loss at 8p is associated with progression from noninvasive intraepithelial neoplasm to invasive carcinoma. DUSP4 re-expression in pancreatic cancer cell lines, invasion/anoikis assays, MEK inhibitor in orthotopic xenograft Cancer research Medium 26941286
2016 Induced DUSP4 expression in triple-negative breast cancer cells blocks cell cycle at G1/S checkpoint and inhibits ERK1/2, p38, JNK1, RB, and NFκB p65 phosphorylation, as well as in vitro and in vivo growth and invasiveness. Protein microarray of 172 phosphoproteins was used to map DUSP4-regulated signaling. DUSP4 overexpression, protein/phosphoprotein microarray (172 proteins), cell cycle analysis, in vivo xenograft, invasion assays Breast cancer research and treatment Medium 27393618
2017 DUSP4 associates with GR (glucocorticoid receptor) and JNK1 in a complex, dephosphorylates JNK1, and prevents phosphorylation of GR at Ser226 (which impairs GR nuclear translocation). DUSP4 knockdown enhanced JNK1 and GR-Ser226 phosphorylation, reduced GR nuclear translocation, and decreased corticosteroid sensitivity. Formoterol enhanced DUSP4 phosphatase activity and restored corticosteroid sensitivity reduced by DUSP4 siRNA. Co-immunoprecipitation of DUSP4-GR-JNK1, siRNA knockdown, fluorescence-based IP-DUSP4 phosphatase activity assay, imaging flow cytometry for GR nuclear translocation, Western blot for phospho-JNK1 and phospho-GR-Ser226 Molecular pharmacology High 28283554
2018 Compound heterozygous deletion of Dok2 and Dusp4 in mice results in lung tumorigenesis with short latency and high incidence, synergistically activating MAPK signaling and promoting cell proliferation. Restoration of both DOK2 and DUSP4 in lung cancer cells suppressed MAPK activation and cell proliferation. Mouse ortholog compound heterozygous knockout, lung tumor incidence monitoring, MAPK signaling assays in primary cells and cell lines, DOK2/DUSP4 restoration experiments The Journal of clinical investigation High 30475228
2019 VIP signaling in the suprachiasmatic nucleus (SCN) requires ERK1/2 activity and is tuned by DUSP4 as a negative regulator to drive circadian re-programming. ERK1/2 and DUSP4 are critical elements of VIP-directed synchronization of SCN circadian oscillations. SCN organotypic slice culture with VIP treatment, ERK inhibition, transcriptional profiling, circadian clock assays Nature communications Medium 30710088
2019 DUSP4 expression is induced by PDGF-BB in an ERK1/2-, STAT3-, and p53-dependent manner. ERK1/2 inhibition reduced DUSP4 mRNA levels; STAT3 was necessary for maintaining p53 expression; and p53, which has binding sites in the DUSP4 promoter, was found to promote DUSP4 transcription. PDGF-BB stimulation, ERK/STAT3/p53 inhibitors and knockdown, DUSP4 mRNA quantification, promoter binding analysis Biochemical and biophysical research communications Medium 31526568
2019 Diabetes-induced reduction of DUSP4 in podocytes enhances p38 and JNK activity and podocyte dysfunction. DUSP4 overexpression prevented activation of p38, JNK, caspase 3/7, and NADPH oxidase 4 (Nox4) expression induced by high glucose. DUSP4-/- diabetic mice showed exacerbated albuminuria, mesangial expansion, glomerular fibrosis, podocyte foot process effacement, and sustained p38/JNK activation. PKC-δ inhibition prevented DUSP4 expression decline. DUSP4 overexpression in cultured podocytes, DUSP4-/- diabetic mouse model, PKC-δ inhibitor, Western blot for p38/JNK/caspase-3/Nox4, glomerular histology Diabetes High 30862678
2020 ΔNp63α induces DUSP4 expression in endometrial epithelial cells, activating a DUSP4/GSK-3β/SNAI1 pathway that drives epithelial-mesenchymal transition (EMT). bFGF reversed ΔNp63α-induced EMT and endometrial fibrosis by blocking this pathway. ΔNp63α forced expression in endometrial epithelial cells, transcriptomic analysis, Western blot for GSK-3β/SNAI1, bFGF rescue in vitro and in vivo Cell death & disease Medium 32528070
2021 DUSP4 transcriptionally modulates DUSP4 expression through STAT3 and YY1 binding sites in DUSP4 promoters. CTCF stimulated promoter 2 activity while STAT3 stimulated promoter 1 activity; YY1 positively regulated both promoters. Functionality of YY1 binding sites confirmed by site-directed mutagenesis. Luciferase reporter assays, site-directed mutagenesis of TF binding sites, in silico prediction of binding sites Journal of cellular biochemistry Medium 34254709
2022 ARID1A loss in endometrial epithelial cells downregulates DUSP4 via decreased histone acetylation marks (H3K27Ac, H3K9Ac) on DUSP4 regulatory regions, leading to MAPK pathway activation. Ectopic DUSP4 expression decreased cell proliferation, and pharmacological MAPK pathway inhibition mitigated tumor formation in vivo. RNA-seq of ARID1A-deficient cells, ChIP-seq for H3K27Ac/H3K9Ac on DUSP4 locus, DUSP4 ectopic expression, MEK inhibitor in vivo, genetically engineered mouse models Journal of biomedical science High 38071325
2022 DUSP4 depletion in BRAF/NRAS-mutant melanoma leads to toxic levels of MAPK hyperactivation (oncogene overdose) and downregulation of lineage-defining genes including MITF. This phenotype occurs in both drug-naive and drug-resistant melanoma cells. DUSP4 depletion in melanoma cell lines, ERK/MAPK activation assays, MITF and lineage gene expression analysis Life science alliance Medium 35580987
2022 DUSP4 inactivation in melanoma unexpectedly leads to reduced ERK1/2 phosphorylation rather than ERK activation, through upregulation of DUSP6 at a post-transcriptional level. DUSP6 knockout eliminated the DUSP4-depletion effect on ERK activity and cell growth, placing DUSP4 upstream of DUSP6 in ERK regulation in melanoma. DUSP4 depletion and DUSP6 knockout in melanoma lines, kinase translocation reporter for ERK activity, immunoblotting for DUSP4/DUSP6/pERK The Journal of investigative dermatology Medium 35189148
2022 MKP-2 (DUSP4) is upregulated in obesity and fatty liver disease. MKP-2 deficient mice are protected against diet-induced obesity and hepatic steatosis with improved insulin sensitivity. Loss of MKP-2 enhanced p38, JNK, and ERK activities in insulin-responsive tissues and was associated with enhanced Akt activity linked to downregulated PTEN in liver. MKP-2 KO mice on high-fat diet, glucose/insulin tolerance tests, PTEN/Akt/MAPK Western blots, respiratory exchange ratio measurement Nutrients Medium 35745205
2023 DUSP4 directly binds HSP90β and dephosphorylates it at T214 and Y216, promoting HSP90β ATPase activity. These dephosphorylation events stabilize JAK1/2-STAT3 signaling and promote p-STAT3(Y705) nuclear translocation in esophageal squamous cell carcinoma. HSP90β inhibitor NVP-BEP800 inhibited PDX tumor growth and inactivated JAK1/2-STAT3 signaling. Co-IP/pulldown of DUSP4-HSP90β, phospho-site mapping (T214/Y216), ATPase activity assay, HSP90β inhibitor treatment, in vivo PDX model, Dusp4 KO mouse in carcinogen model Cell reports High 37141098
2024 DUSP4 forms a signaling complex with TBK1, ERK1/2, and IRF3 and regulates TBK1 and ERK1/2 activation to modulate production of type I interferons downstream of RIG-I and STING nucleic acid sensors. DUSP4-deficient mice were more resistant to RNA and DNA virus infections but more susceptible to malaria parasites. Co-IP identifying DUSP4-TBK1-ERK1/2-IRF3 complex, DUSP4-/- mouse infection models (RNA virus, DNA virus, malaria parasite), type I IFN measurement Cell death and differentiation High 38383887
2024 DUSP4 interacts with ALDOB (aldolase B) and dephosphorylates it, thereby inhibiting G6PD (glucose-6-phosphate dehydrogenase) activity and the ROS/pentose phosphate pathway in HER2-positive breast cancer cells. Co-IP and mass spectrometry (IP-MS) identifying DUSP4-ALDOB interaction, DUSP4 KO cells, G6PD activity assay, ROS measurement, RNA-seq of KO cells Translational oncology Medium 38843658
2025 DUSP4 dephosphorylates p-ERK and disrupts ERK-PGK1 interaction, reducing PGK1 S203 phosphorylation and its mitochondrial localization, thereby decreasing lactate production and increasing ROS levels in ovarian cancer cells. Phosphoproteomic profiling identified MAPK pathway and cellular metabolism as key downstream targets of DUSP4. LC-MS/MS phosphoproteomic profiling of DUSP4 overexpressing cells, PGK1 co-immunoprecipitation with ERK, mitochondrial fractionation, lactate/ROS assays, in vivo mouse tumor model Cancer cell international Medium 40082940
2025 DUSP4 suppresses ferroptosis in MSI colorectal cancer cells by reducing lipid peroxidation and inhibiting intracellular Fe2+ accumulation through downregulation of transferrin receptor (TFRC), which is transcriptionally regulated by c-MYC. DUSP4 also dephosphorylates CDK7, promoting CXCL16 expression and CD8+ T cell infiltration. Ferroptosis assays (lipid peroxidation, MDA, 4-HNE, Fe2+), phosphoproteomic analysis, TFRC/c-MYC expression studies, cytokine array, CDK7 dephosphorylation assay, flow cytometry for CD8+ T cells British journal of cancer Medium 40847010

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 The mitogen-activated protein kinase phosphatases PAC1, MKP-1, and MKP-2 have unique substrate specificities and reduced activity in vivo toward the ERK2 sevenmaker mutation. The Journal of biological chemistry 391 8626452
2012 Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance. Nature medicine 220 22683778
2009 An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors. Oncogene 194 19525976
1995 Isolation and characterization of a novel dual specific phosphatase, HVH2, which selectively dephosphorylates the mitogen-activated protein kinase. The Journal of biological chemistry 174 7535768
2010 Mutated KRAS results in overexpression of DUSP4, a MAP-kinase phosphatase, and SMYD3, a histone methyltransferase, in rectal carcinomas. Genes, chromosomes & cancer 172 20725992
2013 Activation of MAPK pathways due to DUSP4 loss promotes cancer stem cell-like phenotypes in basal-like breast cancer. Cancer research 135 23966295
2012 Oncogenic KRAS and BRAF activation of the MEK/ERK signaling pathway promotes expression of dual-specificity phosphatase 4 (DUSP4/MKP2) resulting in nuclear ERK1/2 inhibition. Oncogene 76 22430215
2018 MiR-122-5p inhibits cell migration and invasion in gastric cancer by down-regulating DUSP4. Cancer biology & therapy 75 29509059
2006 Inhibition of gluconeogenesis through transcriptional activation of EGR1 and DUSP4 by AMP-activated kinase. The Journal of biological chemistry 68 16849326
2010 Epigenetic downregulation of mitogen-activated protein kinase phosphatase MKP-2 relieves its growth suppressive activity in glioma cells. Cancer research 63 20124482
1995 Isolation and characterisation of a uniquely regulated threonine, tyrosine phosphatase (TYP 1) which inactivates ERK2 and p54jnk. Oncogene 58 8545112
2015 DUSP4 deficiency caused by promoter hypermethylation drives JNK signaling and tumor cell survival in diffuse large B cell lymphoma. The Journal of experimental medicine 56 25847947
2014 Inhibition of G9a induces DUSP4-dependent autophagic cell death in head and neck squamous cell carcinoma. Molecular cancer 56 25027955
2012 Expression of the MAP kinase phosphatase DUSP4 is associated with microsatellite instability in colorectal cancer (CRC) and causes increased cell proliferation. International journal of cancer 56 22965873
2011 DUSP4 deficiency enhances CD25 expression and CD4+ T-cell proliferation without impeding T-cell development. European journal of immunology 54 22101742
2017 IL4 Primes the Dynamics of Breast Cancer Progression via DUSP4 Inhibition. Cancer research 53 28400477
2011 Deletion of the dual specific phosphatase-4 (DUSP-4) gene reveals an essential non-redundant role for MAP kinase phosphatase-2 (MKP-2) in proliferation and cell survival. The Journal of biological chemistry 50 21317287
2019 Vasoactive intestinal peptide controls the suprachiasmatic circadian clock network via ERK1/2 and DUSP4 signalling. Nature communications 48 30710088
2022 Genome-Wide CRISPR/Cas9 Library Screening Identified that DUSP4 Deficiency Induces Lenvatinib Resistance in Hepatocellular Carcinoma. International journal of biological sciences 47 35864956
2016 Genomic Loss of DUSP4 Contributes to the Progression of Intraepithelial Neoplasm of Pancreas to Invasive Carcinoma. Cancer research 45 26941286
2020 ΔNp63α-induced DUSP4/GSK3β/SNAI1 pathway in epithelial cells drives endometrial fibrosis. Cell death & disease 44 32528070
2016 Sanguinarine inhibits growth and invasion of gastric cancer cells via regulation of the DUSP4/ERK pathway. Journal of cellular and molecular medicine 43 27957827
2015 DUSP4-mediated accelerated T-cell senescence in idiopathic CD4 lymphopenia. Blood 43 25733583
2017 DUSP4 promotes doxorubicin resistance in gastric cancer through epithelial-mesenchymal transition. Oncotarget 42 29212207
2015 Modulation of p38 kinase by DUSP4 is important in regulating cardiovascular function under oxidative stress. Free radical biology & medicine 41 26184564
2019 Diabetes-Induced DUSP4 Reduction Promotes Podocyte Dysfunction and Progression of Diabetic Nephropathy. Diabetes 40 30862678
2013 Decreased expression of DUSP4 is associated with liver and lung metastases in colorectal cancer. Medical oncology (Northwood, London, England) 37 23749251
2020 Nonenzymatic function of Aldolase A downregulates miR-145 to promote the Oct4/DUSP4/TRAF4 axis and the acquisition of lung cancer stemness. Cell death & disease 34 32188842
2014 DUSP4 regulates neuronal differentiation and calcium homeostasis by modulating ERK1/2 phosphorylation. Stem cells and development 32 25397900
2008 Transcriptional profiling of endogenous germ layer precursor cells identifies dusp4 as an essential gene in zebrafish endoderm specification. Proceedings of the National Academy of Sciences of the United States of America 32 18719100
2016 Statins affect ETS1-overexpressing triple-negative breast cancer cells by restoring DUSP4 deficiency. Scientific reports 30 27604655
2020 MiR-122-5p protects against acute lung injury via regulation of DUSP4/ERK signaling in pulmonary microvascular endothelial cells. Life sciences 29 32470454
2020 DUSP4 is involved in the enhanced proliferation and survival of DUSP4-overexpressing cancer cells. Biochemical and biophysical research communications 28 32505357
2017 DUSP4 is associated with increased resistance against anti-HER2 therapy in breast cancer. Oncotarget 28 29100381
2012 Mitogen-activated protein kinase phosphatase 2, MKP-2, regulates early inflammation in acute lung injury. American journal of physiology. Lung cellular and molecular physiology 27 22683570
2019 Unraveling the role of H3K4 trimethylation and lncRNA HOTAIR in SATB1 and DUSP4-dependent survival of virulent Mycobacterium tuberculosis in macrophages. Tuberculosis (Edinburgh, Scotland) 26 32090865
2016 Analysis of phosphatases in ER-negative breast cancers identifies DUSP4 as a critical regulator of growth and invasion. Breast cancer research and treatment 26 27393618
2018 Compound haploinsufficiency of Dok2 and Dusp4 promotes lung tumorigenesis. The Journal of clinical investigation 25 30475228
1997 Chromosomal localization of three human dual specificity phosphatase genes (DUSP4, DUSP6, and DUSP7). Genomics 25 9205128
2019 Dual-specificity protein phosphatase DUSP4 regulates response to MEK inhibition in BRAF wild-type melanoma. British journal of cancer 24 31839677
2017 Nimbolide suppresses non-small cell lung cancer cell invasion and migration via manipulation of DUSP4 expression and ERK1/2 signaling. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 24 28554129
2019 Estradiol inhibits fMLP-induced neutrophil migration and superoxide production by upregulating MKP-2 and dephosphorylating ERK. International immunopharmacology 23 31401382
2010 Post-translational regulation of mitogen-activated protein kinase phosphatase-2 (MKP-2) by ERK. Cell cycle (Georgetown, Tex.) 23 21084841
2023 DUSP4 promotes esophageal squamous cell carcinoma progression by dephosphorylating HSP90β. Cell reports 22 37141098
2019 miR-1226-3p Promotes Sorafenib Sensitivity of Hepatocellular Carcinoma via Downregulation of DUSP4 Expression. Journal of Cancer 22 31258782
2019 GFAP alternative splicing regulates glioma cell-ECM interaction in a DUSP4-dependent manner. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 31480854
2014 Redox activation of DUSP4 by N-acetylcysteine protects endothelial cells from Cd²⁺-induced apoptosis. Free radical biology & medicine 21 24973647
2022 Dual-Specificity Protein Phosphatase 4 (DUSP4) Overexpression Improves Learning Behavior Selectively in Female 5xFAD Mice, and Reduces β-Amyloid Load in Males and Females. Cells 18 36497141
2016 DUSP4/MKP2 overexpression is associated with BRAF(V600E) mutation and aggressive behavior of papillary thyroid cancer. OncoTargets and therapy 18 27143921
2023 ARID1A loss activates MAPK signaling via DUSP4 downregulation. Journal of biomedical science 17 38071325
2014 Post-translational regulation of mitogen-activated protein kinase phosphatase (MKP)-1 and MKP-2 in macrophages following lipopolysaccharide stimulation: the role of the C termini of the phosphatases in determining their stability. The Journal of biological chemistry 17 25204653
2012 MKP-2: out of the DUSP-bin and back into the limelight. Biochemical Society transactions 17 22260697
2024 DUSP4 modulates RIG-I- and STING-mediated IRF3-type I IFN response. Cell death and differentiation 16 38383887
2020 DUSP4 appears to be a highly localized endogenous inhibitor of epileptic signaling in human neocortex. Neurobiology of disease 16 32890776
2013 MAPK phosphatase-2 (MKP-2) is induced by hCG and plays a role in the regulation of CYP11A1 expression in MA-10 Leydig cells. Endocrinology 16 23471219
2022 DUSP4 protects BRAF- and NRAS-mutant melanoma from oncogene overdose through modulation of MITF. Life science alliance 15 35580987
2022 Metabolic Impact of MKP-2 Upregulation in Obesity Promotes Insulin Resistance and Fatty Liver Disease. Nutrients 15 35745205
2003 The I(1)-imidazoline receptor in PC12 pheochromocytoma cells reverses NGF-induced ERK activation and induces MKP-2 phosphatase. Brain research 15 12865160
2023 ADSC secretome constrains NK cell activity by attenuating IL-2-mediated JAK-STAT and AKT signaling pathway via upregulation of CIS and DUSP4. Stem cell research & therapy 14 37964351
2022 SIRT3 inhibitor 3-TYP exacerbates thioacetamide-induced hepatic injury in mice. Frontiers in physiology 13 35923224
2021 DUSP4 alleviates LPS-induced chondrocyte injury in knee osteoarthritis via the MAPK signaling pathway. Experimental and therapeutic medicine 13 34650647
2014 Functional analysis of MKP-1 and MKP-2 in breast cancer tamoxifen sensitivity. Oncotarget 13 24658355
2002 The carboxyl-terminal domains of MKP-1 and MKP-2 have inhibitory effects on their phosphatase activity. Molecular and cellular biochemistry 13 12083364
2021 miR‑122‑5p suppresses the oncogenesis of PTC by inhibiting DUSP4 expression. Molecular medicine reports 12 33760201
2017 Impaired Dual-Specificity Protein Phosphatase DUSP4 Reduces Corticosteroid Sensitivity. Molecular pharmacology 12 28283554
2012 MEK inhibition as a strategy for targeting residual breast cancer cells with low DUSP4 expression. Breast cancer research : BCR 12 23127286
2022 Reduction of DUSP4 contributes to podocytes oxidative stress, insulin resistance and diabetic nephropathy. Biochemical and biophysical research communications 11 35940125
2021 The microRNA-429/DUSP4 axis regulates the sensitivity of colorectal cancer cells to nintedanib. Molecular medicine reports 11 33495832
2020 DUSP4 directly deubiquitinates and stabilizes Smad4 protein, promoting proliferation and metastasis of colorectal cancer cells. Aging 11 32897241
2023 DUSP4 inhibits autophagic cell death and apoptosis in colorectal cancer by regulating BCL2-Beclin1/Bax signaling. Molecular biology reports 10 36705792
2022 DUSP4 Silencing Enhances the Sensitivity of Breast Cancer Cells to Doxorubicin through the Activation of the JNK/c-Jun Signalling Pathway. Molecules (Basel, Switzerland) 10 36234680
2019 Dual specificity phosphatase (DUSP)-4 is induced by platelet-derived growth factor -BB in an Erk1/2-, STAT3- and p53-dependent manner. Biochemical and biophysical research communications 9 31526568
2015 Ethanolic extract of Allium cepa stimulates glucose transporter typ 4-mediated glucose uptake by the activation of insulin signaling. Planta medica 9 25654406
2022 Combined Dusp4 and p53 loss with Dbf4 amplification drives tumorigenesis via cell cycle restriction and replication stress escape in breast cancer. Breast cancer research : BCR 8 35850776
2021 DUSP4 inhibits autophagic cell death in PTC by inhibiting JNK-BCL2-Beclin1 signaling. Biochemistry and cell biology = Biochimie et biologie cellulaire 8 33621155
2021 DUSP4 promotes the carcinogenesis of CCRCC via negative regulation of autophagic death. Bioscience, biotechnology, and biochemistry 8 34143206
2021 Lysine-Specific Histone Demethylase 1 Promotes Oncogenesis of the Esophageal Squamous Cell Carcinoma by Upregulating DUSP4. Biochemistry. Biokhimiia 8 34937541
2020 Aberrant expression of DUSP4 is a specific phenomenon in betel quid-related oral cancer. Medical molecular morphology 8 32951127
2020 Dusp4 Contributes to Anesthesia Neurotoxicity via Mediated Neural Differentiation in Primates. Frontiers in cell and developmental biology 8 32974341
2013 T cell hypo-responsiveness against Leishmania major in MAP kinase phosphatase (MKP) 2 deficient C57BL/6 mice does not alter the healer disease phenotype. PLoS neglected tropical diseases 7 23437409
2023 DOCK1 insufficiency disrupts trophoblast function and pregnancy outcomes via DUSP4-ERK pathway. Life science alliance 6 37967942
2021 SAHA could inhibit TGF-β1/p38 pathway in MI-induced cardiac fibrosis through DUSP4 overexpression. Heart and vessels 6 34236463
2021 Transcriptional regulation of human DUSP4 gene by cancer-related transcription factors. Journal of cellular biochemistry 6 34254709
2022 Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinoma. Cell death discovery 5 36127345
2021 Nicotine-derived NNK induces the stemness enrichment of CRC cells through regulating the balance of DUSP4-ERK1/2 feedback loop. Ecotoxicology and environmental safety 5 33662786
2025 DUSP4 inhibited tumor cell proliferation by downregulating glycolysis via p-ERK/p-PGK1 signaling in ovarian cancer. Cancer cell international 4 40082940
2025 The transcription factor PITX1 cooperates with super-enhancers to regulate the expression of DUSP4 and inhibit pyroptosis in pulmonary artery smooth muscle cells. Respiratory research 4 40241046
2025 Exosomal miR-122-5p for regulation of secretory functions of fibroblasts and promotion of breast cancer metastasis by targeting MKP-2: an experimental study. Cancer biology & therapy 4 40320567
2024 DUSP4 enhances therapeutic sensitivity in HER2-positive breast cancer by inhibiting the G6PD pathway and ROS metabolism by interacting with ALDOB. Translational oncology 4 38843658
2023 Identification of DUSP4/6 overexpression as a potential rheostat to NRAS-induced hepatocarcinogenesis. BMC cancer 4 37946160
2022 Long non-coding RNA AFAP1-AS1 promotes thyroid cancer progression by sponging miR-204-3p and upregulating DUSP4. Journal of biochemistry 4 34652441
2022 DUSP4 Inactivation Leads to Reduced Extracellular Signal‒Regulated Kinase Activity through Upregulation of DUSP6 in Melanoma Cells. The Journal of investigative dermatology 4 35189148
2022 ING4 Promotes Stemness Enrichment of Human Renal Cell Carcinoma Cells Through Inhibiting DUSP4 Expression to Activate the p38 MAPK/type I IFN-Stimulated Gene Signaling Pathway. Frontiers in pharmacology 4 35496267
2022 TAT-Beclin 1 represses the carcinogenesis of DUSP4-positive PTC by enhancing autophagy. Molecular biology reports 4 36474060
2020 Candidate Causal Variants at the 8p12 Breast Cancer Risk Locus Regulate DUSP4. Cancers 4 31936698
2020 Expression of DUSP4 transcript variants as a potential biomarker for colorectal cancer. Biomarkers in medicine 4 32613839
1977 [Structures of oncornaviruses of C-typ-negativ staining technique by electron microscopy (author's transl)]. Archiv fur Geschwulstforschung 4 72553
2025 The novel role of DUSP4 in suppressing ferroptosis and promoting cytotoxicity of CD8+ T cells in MSI colorectal cancer. British journal of cancer 2 40847010
2024 Proteomic Signaling of Dual-Specificity Phosphatase 4 (DUSP4) in Alzheimer's Disease. Biomolecules 2 38254666
2022 Investigating the Role of DUSP4 in Uveal Melanoma. Translational vision science & technology 2 36576731

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