Affinage

DUSP1

Dual specificity protein phosphatase 1 · UniProt P28562

Length
367 aa
Mass
39.3 kDa
Annotated
2026-06-09
100 papers in source corpus 48 papers cited in narrative 47 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DUSP1 (CL100/MKP-1) is a dual-specificity phosphatase that serves as the principal inducible negative-feedback regulator of MAPK signaling, dephosphorylating both phosphothreonine and phosphotyrosine residues on ERK, JNK, and p38 in an active-site Cys258-dependent manner (PMID:8390041). Its substrate engagement is cell-type- and stimulus-specific: in fibroblasts DUSP1 inactivates ERK following EGF, whereas in other lineages this role is filled by PP2A and distinct tyrosine phosphatases (PMID:7780739). By selectively suppressing JNK or p38, DUSP1 controls divergent outcomes including protection from UV- and cisplatin-induced apoptosis (PMID:9501207, PMID:11064451), oxidative-stress survival (PMID:15059639), BDNF-driven axon branching through JNK-dependent microtubule stabilization (PMID:20935641), adipogenesis via ERK inactivation (PMID:15269202), and steroidogenesis through nuclear and mitochondrial ERK control of the StAR axis (PMID:21558315). DUSP1 expression is regulated at every level: transcriptionally by glucocorticoids (PMID:11742987), E2F-1 (PMID:17638884), progesterone receptor (PMID:22020934), and ATF4 (whose CRE binding is blocked by PARP-1-mediated PARylation) (PMID:28457938); post-transcriptionally through p38-MK2 signaling and mRNA stabilization/translation by HuR and NF90 (PMID:16978838, PMID:18490444); and post-translationally, where ERK2 and PKA phosphorylation and acetylation modulate stability and substrate binding (PMID:18089824, PMID:12506119, PMID:18922786) while ubiquitin-proteasome degradation is opposed by the deubiquitinases STAMBPL1 and USP49 (PMID:35236965, PMID:30246457). Beyond canonical MAPK targets, DUSP1 directly binds and dephosphorylates VCP at Ser784 on mitochondria to support mitochondrial quality control (PMID:37464072) and binds JNK to prevent BAX-mediated mtDNA release and cGAS-STING activation (PMID:37935658). Through these mechanisms DUSP1 governs innate and adaptive immunity (PMID:19748894, PMID:25312268), tissue repair (PMID:21987635), glycolytic reprogramming via p38→PFKFB3 (PMID:36803959), and disease contexts including cancer chemoresistance (PMID:16462770, PMID:28319094), neurodegeneration (PMID:23392662, PMID:31840000), and depression-like behavior (PMID:31267372, PMID:38424085).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1993 High

    Established the foundational biochemical identity of DUSP1 as a dual-specificity phosphatase that directly inactivates MAP kinase, answering whether CL100 was itself the enzyme acting on both phospho-Thr and phospho-Tyr.

    Evidence In vitro phosphatase assay with recombinant protein, active-site Cys258 mutagenesis, and cell-free Xenopus extract epistasis

    PMID:8390041

    Open questions at the time
    • Did not establish which MAPK family members are physiological substrates in vivo
    • No structural basis for dual specificity
  2. 1995 High

    Defined the cell-type specificity and physiological scope of DUSP1's ERK-inactivating role, showing it is not the universal MAPK phosphatase since other phosphatases dominate in some lineages.

    Evidence Cycloheximide depletion, phospho-specific western blotting, and PP2A activity assays across multiple cell lines

    PMID:7780739

    Open questions at the time
    • Did not resolve what determines lineage-specific phosphatase usage
    • Loss of DUSP1 by cycloheximide is indirect
  3. 2000 High

    Demonstrated that DUSP1 selectively targets JNK over p38 to suppress stress-induced apoptosis and that enzymatic activity is essential, distinguishing it functionally from ERK-specific phosphatases.

    Evidence Conditional and catalytically inactive mutant overexpression with JNK/p38 kinase and apoptosis assays in UV- and cisplatin-treated cells

    PMID:11064451 PMID:9501207

    Open questions at the time
    • Did not explain the molecular basis of JNK substrate selectivity
    • Endogenous DUSP1 contribution not tested by knockout
  4. 2001 High

    Revealed that DUSP1 is regulated transcriptionally and through protein stability, with glucocorticoids acting at both the promoter and proteasomal-degradation levels in a cell-type-dependent manner.

    Evidence Promoter reporters, proteasome inhibition, protein stability and ERK kinase assays in mast cells versus fibroblasts

    PMID:11742987

    Open questions at the time
    • The degradation machinery and signal controlling proteasomal turnover were unidentified
    • Glucocorticoid promoter elements not mapped
  5. 2007 High

    Mapped specific transcription factors controlling DUSP1 induction, establishing E2F-1, and later PR, as direct promoter-binding activators linking DUSP1 to stress-induced ERK control and proliferation outcomes.

    Evidence ChIP, luciferase reporters, ectopic factor expression with phospho-ERK readout in oxidative-stress and breast cancer cells

    PMID:17638884 PMID:22020934

    Open questions at the time
    • Combinatorial control among transcription factors not integrated
    • Stimulus-specificity of factor recruitment unresolved
  6. 2008 High

    Defined post-transcriptional and post-translational control layers, showing HuR/NF90 stabilize DUSP1 mRNA and that acetylation reprograms substrate engagement toward p38.

    Evidence RNP-immunoprecipitation, biotinylated RNA pulldown, siRNA of RNA-binding proteins, and acetylation/Co-IP analyses with phospho-MAPK readouts

    PMID:18490444 PMID:18922786

    Open questions at the time
    • The acetyltransferase/deacetylase enzymes were not identified
    • Crosstalk between mRNA stabilization and PTMs unexamined
  7. 2009 High

    Genetic knockout work established DUSP1 as a physiological in vivo regulator of immunity, showing it is a positive regulator of T cell activation via JNK and NFATc1 control.

    Evidence Mkp-1-/- mice with in vitro T cell assays and in vivo influenza and EAE models

    PMID:19748894

    Open questions at the time
    • Cell-intrinsic versus systemic contributions not fully dissected
    • Mechanism linking JNK to NFAT translocation incomplete
  8. 2010 High

    Knockout neurons revealed a developmental role: DUSP1 enables BDNF-induced axon branching through spatiotemporal JNK inactivation that protects microtubules.

    Evidence mkp-1 null neurons, JNK substrate phosphorylation assays, and axon branching quantification

    PMID:20935641

    Open questions at the time
    • Spatial mechanism of localized JNK inactivation unresolved
    • Identity of microtubule-destabilizing substrates only inferred
  9. 2011 High

    Defined DUSP1's role in tuning inflammatory timing and tissue repair, showing it restrains p38 to permit the pro- to anti-inflammatory macrophage transition via a p38→miR-21→PTEN→AKT cascade.

    Evidence MKP-1 knockout mice with p38 kinase, miR-21/PTEN/AKT readouts and pharmacological p38 rescue

    PMID:21987635

    Open questions at the time
    • Macrophage-intrinsic versus other cell contributions not separated
    • Direct vs indirect control of miR-21 induction not resolved
  10. 2012 High

    Substrate-binding mutant analysis dissected which MAPKs mediate DUSP1 neuroprotection, showing p38 and JNK inhibition additively protect striatal neurons from polyglutamine toxicity independent of ERK.

    Evidence Lentiviral wild-type and selective binding-domain mutants with caspase and MAPK phosphorylation readouts in vitro and in an HD rat model

    PMID:23392662

    Open questions at the time
    • Structural basis of selective MAPK binding not determined
    • Translatability to chronic disease timescales untested
  11. 2016 High

    Knockout and knockdown studies expanded DUSP1's mechanistic reach to autophagy and inflammatory gene stability, showing it suppresses the class III PtdIns3K complex via ERK and maintains IRF1-dependent gene expression.

    Evidence DUSP1 knockout MEFs and shRNA with autophagic flux, ULK1/BECN1 phosphorylation, Co-IP, and IRF1 mRNA stability/ChIP assays

    PMID:27459239 PMID:27551049

    Open questions at the time
    • Direct versus MAPK-mediated effects on autophagy machinery only partially separated
    • How DUSP1 stabilizes IRF1 mRNA mechanistically unresolved
  12. 2017 High

    Established DUSP1 as a determinant of cancer therapy resistance and uncovered ATF4/PARP-1 transcriptional control, linking growth-factor-induced DUSP1 to TKI efficacy thresholds and chemoresistance.

    Evidence Fos/Dusp1 knockout mice, pharmacological DUSP1 inhibition, patient-derived CML xenografts, and in vitro PARylation/ChIP-qPCR of ATF4 at the promoter

    PMID:28319094 PMID:28457938 PMID:28650468

    Open questions at the time
    • Selectivity and mechanism of pharmacological DUSP1 inhibitors not fully defined
    • Generalizability of the ATF4-PARP-1 axis across stimuli unclear
  13. 2018 High

    Identified the deubiquitinases USP49 and (later) STAMBPL1 that counteract DUSP1 degradation and uncovered a DUSP1-Nrf2 antioxidant feedback loop, resolving how DUSP1 protein abundance is set.

    Evidence Co-IP, ubiquitination assays, DUB screen, domain-mapped Nrf2 interaction, ARE reporters and knockout colitis/I-R models

    PMID:30061089 PMID:30246457 PMID:35236965

    Open questions at the time
    • E3 ligases driving DUSP1 ubiquitination remain unidentified
    • Hierarchy among competing stability mechanisms unknown
  14. 2023 High

    Expanded DUSP1's substrate repertoire beyond MAPKs by demonstrating direct dephosphorylation of VCP at Ser784 and JNK-binding control of BAX-mediated mtDNA release/cGAS-STING activation, establishing mitochondrial quality-control functions.

    Evidence Co-IP, phosphomimetic VCP mutant, Dusp1-/- and Sting-/- mice, mitochondrial imaging and mtDNA release assays

    PMID:37464072 PMID:37935658

    Open questions at the time
    • Whether VCP dephosphorylation is direct catalysis in vivo not fully isolated from MAPK effects
    • Stoichiometry and regulation of mitochondrial DUSP1 pool unknown
  15. 2023 High

    Connected DUSP1 to metabolic reprogramming during sepsis, placing p38 downstream of DUSP1 in control of the glycolytic enzyme PFKFB3 and lactate production.

    Evidence Mkp-1-/- mice, sepsis/LPS models, PFKFB3 western blotting, lactate measurement, and p38 versus JNK pharmacological epistasis

    PMID:36803959

    Open questions at the time
    • Direct transcriptional versus post-transcriptional control of PFKFB3 not separated
    • Cell-type-specific metabolic contributions incompletely mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how DUSP1 substrate selectivity (ERK vs JNK vs p38 vs non-MAPK targets such as VCP) is dynamically encoded by localization, PTM state, and binding partners within a single cell.
  • No structural model explaining dual-specificity catalysis and substrate switching
  • E3 ligase(s) for DUSP1 degradation unidentified
  • Direct non-MAPK catalysis (VCP) not reconstituted in vitro

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0016787 hydrolase activity 2
Localization
GO:0005739 mitochondrion 3 GO:0005634 nucleus 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-162582 Signal Transduction 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-9612973 Autophagy 1

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 CL100/DUSP1, expressed and purified from bacteria, acts as a dual-specificity phosphatase that rapidly and potently inactivates MAP kinase in vitro by concomitant dephosphorylation of both phosphothreonine and phosphotyrosine residues. It also suppresses [val12]ras-induced MAP kinase activation in Xenopus oocyte cell-free extracts. Both activities are abolished by mutagenesis of the conserved active-site Cys-258. In vitro phosphatase assay with recombinant protein; active-site mutagenesis (Cys258); cell-free Xenopus oocyte extract epistasis Oncogene High 8390041
1994 The CL100 gene is present as a single locus and maps to human chromosome 5q34, and CL100-homologous sequences are conserved in mouse, chicken, Xenopus, and Drosophila genomes. PCR with human-rodent somatic cell hybrid DNA panel; fluorescence in situ hybridization (FISH) Human genetics Medium 8168826
1995 In Swiss 3T3 fibroblasts, depletion of CL100/DUSP1 with cycloheximide blocks inactivation of p42 MAP kinase after EGF stimulation; however, in adipose (3T3-L1), chromaffin (PC12), and endothelial (PAE) cells, rapid p42 MAP kinase inactivation is not catalyzed by CL100 but instead by protein phosphatase 2A (dephosphorylating Thr183) and a distinct protein tyrosine phosphatase (dephosphorylating Tyr185). Cycloheximide depletion; phospho-specific antibody western blotting; vanadate inhibition; PP2A activity assay in cell extracts Current biology High 7780739
1995 CL100/DUSP1 mRNA is induced ~4-fold in hippocampus and cerebral cortex within 1 h of reperfusion following transient forebrain ischemia in rats, with expression localized to neuronal cells by in situ hybridization. Northern blotting; in situ hybridization histochemistry Journal of cerebral blood flow and metabolism Low 7798338
1997 In human mesangial cells, CL100/DUSP1 gene expression is induced by activation of the ERK cascade (blocked by MEK antagonist PD098059) and also by the p38/SAPK activator anisomycin (partially blocked by SB203580), demonstrating ERK-dependent and ERK-independent transcriptional induction pathways. Northern blotting; MEK inhibitor (PD098059); p38 inhibitor (SB203580); selective ERK agonists Journal of the American Society of Nephrology Medium 9013447
1998 Conditional expression of MKP-1 abolishes UV-induced SAPK/JNK and p38 MAPK activity, inhibits caspase-3 activation, prevents PARP cleavage, and protects U937 cells against UV-induced apoptosis in a dose-dependent manner. Cytoprotection tracks closely with JNK (not p38) inhibition, as SB203580 had no protective effect. Conditional expression system (metallothionein IIa promoter); SAPK/p38 kinase assays; caspase-3 activity; PARP western blot; DNA fragmentation; morphological apoptosis scoring Proceedings of the National Academy of Sciences High 9501207
2000 Expression of CL100/MKP-1 selectively prevents SAPK/JNK (but not p38) activation by cisplatin and protects cells against cisplatin-induced apoptosis. A catalytically inactive CL100 mutant decreases the IC50 for cisplatin and increases JNK activity, indicating that phosphatase activity is required. ERK-specific phosphatase Pyst1 does not confer protection. Overexpression and dominant-negative mutant transfection; JNK/p38 kinase assays; cell viability (IC50); apoptosis assays Oncogene High 11064451
2000 Glucagon induces MKP-1 mRNA and protein expression in rat hepatocytes through a cAMP/PKA-dependent mechanism (sensitive to adenylate cyclase and PKA inhibitors), and the induced MKP-1 correlates with antagonization of EGF-induced MAP kinase phosphorylation. Northern/Western blotting; pharmacological inhibitors of adenylate cyclase, PKA, PKG, PKC, Ca2+, MAPKs Gastroenterology Medium 10784592
2001 Glucocorticoids inhibit ERK-1/2 in mast cells via a dual mechanism: (1) transcriptional up-regulation of MKP-1 at the promoter level, and (2) inhibition of proteasomal degradation of MKP-1 triggered by mast cell activation. Both actions are necessary for glucocorticoid-mediated ERK-1/2 inhibition. In NIH-3T3 fibroblasts, glucocorticoids up-regulate MKP-1 but do not block its proteasomal degradation, and consequently cannot inhibit ERK-1/2. Promoter reporter assays; proteasome inhibitor experiments; Western blotting for MKP-1 protein stability; ERK-1/2 kinase assays; cell-type comparison The EMBO journal High 11742987
2002 PKA phosphorylates an MKP-1-GST fusion protein in vitro, and cAMP increases 32P incorporation into immunoprecipitated MKP-1 in H295R adrenocortical cells. PKA or MKP-1 overexpression increases CYP17 promoter activity; antisense silencing of MKP-1 attenuates cAMP-stimulated CYP17 expression, while silencing of ERK1/2 increases it, placing MKP-1 in the cAMP/PKA-ERK1/2-SF-1-CYP17 transcriptional axis. In vitro PKA phosphorylation of MKP-1-GST fusion protein; 32P labeling + immunoprecipitation; transient transfection reporter assays; antisense oligonucleotide knockdown The Journal of biological chemistry High 12506119
2004 MKP-1 abundance increases during adipocyte differentiation with timing parallel to decreased p42/p44 MAPK activity. Ectopic MKP-1 expression reduces, and MKP-1 depletion (antisense RNA) increases, p42/p44 MAPK activity. Prevention of MKP-1 up-regulation blocks adipocyte differentiation, an effect reversed by MEK inhibitor PD98059, establishing MKP-1-mediated ERK inactivation as essential for adipogenesis. Ectopic overexpression; antisense RNA knockdown; MEK inhibitor rescue (PD98059); kinase activity assays; differentiation markers The Journal of biological chemistry High 15269202
2004 H2O2 induces MKP-1 expression in rat mesangial cells via the MAP kinase–AP-1 pathway; selective inhibitors of individual MAPKs or dominant-negative c-jun suppress MKP-1 expression. Wild-type MKP-1 but not catalytically inactive MKP-1CS attenuates H2O2-induced apoptosis, establishing that phosphatase activity is required for cytoprotection against oxidative stress. Northern/Western blotting; MAP kinase inhibitors; dominant-negative c-jun; transfection of wild-type vs. catalytically inactive MKP-1CS; apoptosis assay Free radical biology & medicine High 15059639
2004 In normal VSMC, insulin increases MKP-1 expression and MKP-1 phosphorylation (stabilizing it), leading to MAPK inactivation and inhibition of PDGF-driven cell migration. MKP-1 siRNA abolishes insulin inhibition of migration. Adenoviral MKP-1 expression restores insulin inhibition of migration in diabetic GK rat VSMCs, where MKP-1 induction and phosphorylation are impaired. siRNA knockdown; adenoviral overexpression; PDGF-induced migration assay; MAPK phosphorylation western blotting; proteasome inhibitor experiments; cGK Ialpha adenoviral expression American journal of physiology. Cell physiology High 15355857
2006 MKP-1 overexpression increases cisplatin resistance in H-1299 NSCLC cells; siRNA knockdown of MKP-1 sensitizes H-460 cells to cisplatin by enhancing JNK and p38 activation and increasing apoptosis. MKP-1 siRNA-expressing H-460 tumor xenografts grew slower and were more cisplatin-sensitive. Knockdown of the related MKP-2 had no effect, indicating specificity. siRNA knockdown; overexpression; cisplatin sensitivity assay; JNK/p38 kinase western blots; xenograft mouse model Oncogene High 16462770
2006 p38 MAPK mediates MKP-1 induction at a post-transcriptional level in LPS/PGN-stimulated macrophages: pharmacological inhibition or RNAi knockdown of p38 reduces MKP-1 protein but not mRNA; depletion of the p38 substrate MK2 similarly reduces MKP-1, linking p38-MK2 signaling to MKP-1 post-transcriptional regulation and establishing a positive feedback loop. p38 inhibitor (SB203580); RNAi knockdown of p38 and MK2; Northern and Western blotting; LPS tolerance model Cellular signalling Medium 16978838
2007 ERK2 phosphorylates MKP-1 in ovarian cancer cells in response to cisplatin; inhibition of MEK1/2 (U0126) or ERK2 siRNA knockdown decreases cisplatin-induced MKP-1 phosphorylation and reduces MKP-1 protein levels, sensitizing cells to cisplatin. ERK2 knockdown also decreases basal Bcl-2 protein levels. MEK1/2 inhibitor (U0126); siRNA ERK2 knockdown; MKP-1 phosphorylation western blotting; cisplatin sensitivity/apoptosis assays Cancer research Medium 18089824
2007 E2F-1 directly binds to the DUSP1/CL100 promoter at an E2F-1 consensus sequence and a palindromic motif, stimulates DUSP1 promoter activity, and induces DUSP1 expression specifically in response to oxidative stress. E2F-1-induced DUSP1 expression leads to ERK1/2 dephosphorylation and mediates the apoptotic response to oxidative stress. Chromatin immunoprecipitation; luciferase reporter assay; ectopic E2F-1 expression; phospho-ERK western blotting; stress-specific induction experiments Cancer research High 17638884
2008 MKP-1 is acetylated on a key lysine residue following TLR stimulation. Acetylation of MKP-1 promotes its interaction with substrate p38 MAPK, resulting in p38 dephosphorylation and attenuation of innate immunity. Acetylation analysis post-TLR stimulation; interaction/co-immunoprecipitation of acetylated MKP-1 with p38; p38 phosphorylation assays (reviewed/highlighted from primary study) Science signaling Medium 18922786
2008 HuR and NF90 bind to the AU-rich 3' UTR of MKP-1 mRNA. H2O2 treatment increases association of MKP-1 mRNA with HuR and NF90 while decreasing association with translational repressors TIAR and TIA-1. Silencing HuR or NF90 diminishes MKP-1 mRNA stability; HuR silencing also reduces MKP-1 translation. Loss of MKP-1 in HuR-silenced cells leads to elevated phospho-JNK and phospho-p38 after H2O2. Ribonucleoprotein immunoprecipitation; biotinylated RNA pulldown; siRNA silencing of RNA-binding proteins; mRNA stability assays; western blotting for MKP-1 protein and phospho-MAPKs Molecular and cellular biology High 18490444
2008 In pituitary gonadotrophs, overexpression of MKP-1 blocks buserelin (GnRH analogue)-induced ERK dephosphorylation in the nucleus, thereby inhibiting Egr-1 expression; MKP-1 dephosphorylates ERK specifically in the nuclear compartment to control downstream transcription factor activity. Overexpression of MKP-1; chromatin immunoprecipitation (Elk-1 binding to Egr-1 gene); dominant-negative transcription factor mutants; kinase activity assays Journal of cellular biochemistry Medium 18814180
2008 Pancreatic reg I protein physically interacts with MKP-1 as demonstrated by yeast two-hybrid assay and confirmed by immunoprecipitation; high intracellular reg I levels are proposed to bind and inactivate MKP-1. Yeast two-hybrid; co-immunoprecipitation; Northern analysis; microarray The Journal of surgical research Low 18929742
2009 MKP-1 deficiency in T cells impairs activation, proliferation, and function, associated with enhanced JNK activation and reduced NFATc1 nuclear translocation. MKP-1-/- mice are defective in anti-influenza immunity in vivo and resistant to EAE, demonstrating MKP-1 as a positive regulator of T cell activation. Genetic knockout; in vitro T cell activation assays; JNK phosphorylation western blot; NFATc1 nuclear localization; in vivo influenza and EAE models The Journal of biological chemistry High 19748894
2009 Acquired cisplatin resistance in OV433 ovarian cancer cells is associated with increased MKP-1 expression; siRNA knockdown of MKP-1 or its pharmacological inhibitor triptolide resensitizes resistant cells to cisplatin and increases apoptosis. siRNA knockdown; triptolide inhibitor; cisplatin sensitivity and apoptosis assays; western blotting Cell cycle Medium 19755862
2010 BDNF-induced MKP-1 expression in neurons causes spatiotemporal inactivation of JNK, reducing phosphorylation of JNK substrates that destabilize microtubules. Neurons from mkp-1 null mice cannot produce axon branches in response to BDNF, establishing MKP-1 as essential for BDNF-induced axon branching through JNK dephosphorylation. mkp-1 knockout mice; JNK activity assays; phosphorylation of microtubule-destabilizing JNK substrates; axon branching quantification; BDNF treatment Nature neuroscience High 20935641
2011 MKP-1 restricts p38 MAPK activation in macrophages to allow the pro- to anti-inflammatory transition during muscle repair. In MKP-1-deficient macrophages, p38 hyperactivation induces miR-21, which reduces PTEN, thereby extending AKT activation. Temporal p38 inhibition reverses impaired tissue healing in MKP-1-deficient mice. MKP-1 knockout mice; p38 kinase activity assays; miR-21 and PTEN expression; AKT phosphorylation western blotting; p38 inhibitor rescue; tissue repair histology The Journal of cell biology High 21987635
2011 hCG/cAMP stimulation in MA-10 Leydig cells rapidly increases MKP-1 mRNA by transcriptional action and accumulates MKP-1 protein in both nuclear and mitochondrial compartments. hCG/cAMP triggers ERK1/2-dependent MKP-1 phosphorylation. MKP-1 overexpression reduces ERK1/2 phosphorylation, StAR promoter activity, StAR mRNA levels, and steroidogenesis; MKP-1 siRNA knockdown produces opposite effects. mRNA and protein time-course analysis; subcellular fractionation; flag-tagged MKP-1 immunoprecipitation; ERK1/2 phosphorylation western blotting; StAR promoter reporter; siRNA knockdown; steroid hormone measurement Endocrinology High 21558315
2011 Progesterone receptor (PR) acts in a ligand-dependent manner through progesterone response elements downstream of the MKP-1 transcription start site and through Sp1 sites to up-regulate MKP-1 promoter activity. PR-induced MKP-1 expression results in ERK1/2 dephosphorylation and inhibits breast cancer cell proliferation; siRNA knockdown of MKP-1 blocks progestin-mediated ERK1/2 dephosphorylation and anti-proliferative effect. ChIP; luciferase reporter assay; siRNA knockdown of MKP-1; phospho-ERK1/2 western blotting; cell proliferation assay; correlation analysis in 30 breast cancer cell lines The Journal of biological chemistry High 22020934
2012 MKP-1 (DUSP1) enzymatic activity is required for neuroprotection against polyglutamine-expanded huntingtin toxicity in striatal neurons: phosphatase-domain mutants lose protection. Selective MKP-1 mutants that prevent p38 or JNK binding each partially attenuate neuroprotection, demonstrating that both p38 and JNK inhibition additively contribute to MKP-1-mediated neuroprotection without affecting ERK1/2. Lentiviral overexpression of wild-type and selective binding-domain mutants of MKP-1; caspase-3 activation assay; JNK/p38/ERK phosphorylation western blotting; neuronal cell death counting; in vivo rat lentiviral HD model The Journal of neuroscience High 23392662
2012 MKP-1 is essential for RANKL-induced osteoclastogenesis regulation: RANKL induces MKP-1 expression in osteoclast precursors; mkp-1-/- osteoclasts show increased p38 MAPK and JNK activity and hyperactive bone resorption. mkp-1-/- female mice have mildly reduced bone mass, and mkp-1-/- mice show profoundly enhanced osteoclast activation in response to local LPS injection. mkp-1 knockout mice; RANKL stimulation; p38 and JNK phosphorylation western blotting; bone resorption assay; micro-CT bone mass measurement; LPS injection model; osteoclast differentiation assay The American journal of pathology High 19762714
2014 DUSP1 deficiency in mice leads to enhanced oral squamous carcinogenesis (earlier onset, advanced histologic stage) with increased proinflammatory IL-1β production and deregulated chemokines. In a syngeneic tumor model, DUSP1-deficient mice form faster-growing tumors via p38-dependent inflammation, abrogated by p38 inhibitor SB203580. Dusp1-/- mice; 4-NQO carcinogenesis model; syngeneic EO771 tumor model; p38 inhibitor rescue; IL-1β ELISA; bone marrow-derived macrophage ex vivo assays Cancer research High 25312268
2016 DUSP1 overexpression maintains IRF1 mRNA and protein stability by switching off MAPKs; MAPK inhibitors and DUSP1 overexpression prolong IRF1 expression by increasing transcription and mRNA/protein stability. DUSP1 silencing increases MAPK phosphorylation and reduces IRF1 protein levels. IL1B plus dexamethasone-induced DUSP1 maintains expression of IRF1-dependent genes (e.g., CXCL10), contributing to glucocorticoid insensitivity. DUSP1 overexpression and siRNA silencing; MAPK inhibitors; IRF1 mRNA stability assays; phospho-MAPK western blotting; ChIP at CXCL10 promoter; mRNA quantification The Journal of biological chemistry High 27551049
2016 DUSP1 knockdown by shRNA increases both basal and rapamycin-stimulated autophagic flux in ovarian cancer cells and MEFs. DUSP1 knockout promotes phosphorylation of ULK1 (Ser555) and BECN1 (Ser15) and increases association of PIK3C3/VPS34, ATG14, BECN1, and MAPK, activating the class III PtdIns3K complex. DUSP1-mediated suppression of autophagy acts through inactivation of MAPK1-MAPK3 (ERK). shRNA knockdown; DUSP1 knockout MEFs; overexpression; rapamycin treatment; autophagic flux assay; ULK1/BECN1 phosphorylation western blotting; co-immunoprecipitation of autophagy initiation complex components Autophagy High 27459239
2017 PARP-1 activation causes PARylation of ATF4, reducing its binding to the CRE sequence in the MKP-1 promoter; in vitro PARylation assay showed reduced ATF4-CRE binding. PARP inhibition or silencing increases ATF4 nuclear binding and MKP-1 expression (confirmed by ChIP-qPCR showing increased ATF4 occupancy at MKP-1 initiation site), leading to JNK/p38 inactivation, reduced mitochondrial ROS, and decreased cell death. PARP-1 inhibitor/siRNA; in vitro PARylation of ATF4 and EMSA; ChIP-qPCR; MKP-1 western blotting; JNK/p38 phosphorylation; mitochondrial membrane potential; ROS assays; multiple human cell lines Free radical biology & medicine High 28457938
2017 Genetic deletion of Fos and Dusp1 suppresses BCR-ABL-driven CML tumor growth in mice. Pharmacological inhibition of DUSP1 (combined with BCR-ABL TKI and c-FOS inhibition) eradicates minimal residual disease in multiple in vivo and xenograft CML models, indicating that growth-factor-induced DUSP1 expression sets the threshold of TKI efficacy and confers intrinsic resistance. Genetic deletion (Fos/Dusp1 knockout mice); pharmacological DUSP1 inhibition; BCR-ABL mouse model; xenograft with patient-derived CML cells; in vivo tumor growth assays Nature medicine High 28319094
2017 MKP-1 suppresses PARP-1 degradation by inhibiting JNK1/2, which promotes PARP-1 ubiquitination: MKP-1 overexpression increases PARP-1 and PAR protein levels; silencing MKP-1 promotes PARP-1 ubiquitination and reduces PARP-1 levels; silencing JNK1/2 decreases PARP-1 ubiquitination. PARP activity inhibition restores cisplatin sensitivity in MKP-1-overexpressing cells. MKP-1 overexpression and siRNA; JNK1/2 siRNA; ubiquitination assay; PARP-1 protein western blotting; cisplatin sensitivity assay; pharmacological PARP inhibitor Oncogene High 28650468
2018 Mkp-1 directly interacts with the DIDLID motif of Nrf2, increasing Nrf2 stability and positively regulating constitutive and LPS-inducible Nrf2/Ho-1 expression. Conversely, Nrf2 activates Mkp-1 transcription through antioxidant response elements in the Mkp-1 promoter, forming a positive feedback loop that protects against colonic inflammation. Co-immunoprecipitation of Mkp-1-Nrf2 interaction; Mkp-1-/- mice in DSS colitis model; Nrf2/Ho-1 western blotting; ARE promoter reporter for Mkp-1; colitis histology Free radical biology & medicine High 30061089
2018 DUSP1 deficiency activates JNK, which promotes Mff phosphorylation and excessive mitochondrial fission, leading to mitochondrial oxidative stress, mPTP opening, proapoptotic protein leakage, and mitochondria-dependent apoptosis in diabetic nephropathy. DUSP1 overexpression interrupts Mff-related mitochondrial fission and reduces hyperglycemia-mediated mitochondrial damage. DUSP1 overexpression and knockdown; JNK phosphorylation western blotting; Mff phosphorylation; mitochondrial morphology assays; mPTP opening; apoptosis assays; diabetic cell and animal models Journal of cellular physiology Medium 30191967
2018 USP49 deubiquitinates DUSP1, stabilizing DUSP1 protein expression; co-immunoprecipitation confirms direct interaction between USP49 and DUSP1. USP49 overexpression increases DUSP1 levels, reduces JNK1/2 activation, and protects cardiomyocytes against I/R-induced apoptosis; these effects require DUSP1-mediated JNK dephosphorylation. Co-immunoprecipitation; ubiquitination assay; siRNA and overexpression; JNK1/2 western blotting; cell viability and apoptosis assays; in vivo rat I/R model Journal of cellular physiology Medium 30246457
2019 DUSP1 loss in the cochlea of Dusp1-/- mice causes premature progressive hearing loss, hair cell death, spiral neuron degeneration, macrophage infiltration, imbalanced redox status, and dysregulated cytokines, establishing DUSP1 as essential for cochlear homeostasis during aging-related stress responses. Dusp1-/- knockout mice; auditory brainstem response (ABR); histology of cochlear hair cells and spiral neurons; macrophage infiltration quantification; redox status assays; cytokine expression eLife High 30938680
2019 Upregulation of MKP-1 in APP/PS1 transgenic AD mice inhibits APP and BACE1 expression by inactivating the ERK1/2/MAPK signaling pathway, reducing Aβ production and plaque formation, and improving hippocampal LTP and cognitive deficits. Aβ-induced Sp1 activation decreases MKP-1 expression via Sp1 cis-acting binding elements in the MKP-1 promoter. MKP-1 overexpression in APP/PS1 transgenic mice; ERK1/2 phosphorylation western blotting; APP and BACE1 expression; Aβ ELISA; plaque immunostaining; LTP electrophysiology; behavioral cognitive tests; Sp1 promoter analysis Signal transduction and targeted therapy Medium 31840000
2022 STAMBPL1 interacts with MKP-1 and stabilizes it via deubiquitination; a genome-wide siRNA DUB screen identified STAMBPL1 as an MKP-1 deubiquitinase. Both STAMBPL1 and MKP-1 depletion sensitize breast cancer cells to cisplatin by increasing JNK phosphorylation; ectopic MKP-1 overexpression partially rescues STAMBPL1 depletion-induced cisplatin sensitivity. Genome-wide siRNA DUB library screen; co-immunoprecipitation; deubiquitination assay; cisplatin sensitivity; JNK phosphorylation western blotting; in vitro and xenograft studies Oncogene High 35236965
2023 DUSP1 directly binds JNK; DUSP1 deficiency leads to aberrant JNK phosphorylation and BAX translocation to mitochondria, promoting mtDNA leakage and cGAS-STING pathway activation. JNK inhibition or BAX inhibition rescues mtDNA leakage; STING knockout mitigates the adverse effects of DUSP1 deficiency in ischemic AKI. Co-immunoprecipitation of DUSP1-JNK interaction; Dusp1-/- and tubular-specific Sting-/- mice; electron microscopy of mitochondria; mitochondrial membrane potential; BAX translocation western blotting; mtDNA release assay; JNK/BAX inhibitors Cell death & disease High 37935658
2023 DUSP1 interacts with and dephosphorylates VCP at Ser784; the DUSP1 phosphatase domain mediates the DUSP1-VCP interaction on mitochondria, preventing LPS-induced VCP Ser784 phosphorylation. A phosphomimetic VCP mutant abolishes DUSP1-mediated protection of mitochondrial quality control and cardiomyocyte contractility in LPS-induced endotoxemia. Co-immunoprecipitation; phosphomimetic VCP mutant transfection; DUSP1 transgenic mice; LPS endotoxemia model; mitochondrial dynamics and mitophagy assays; echocardiography; western blotting for phospho-VCP Cellular and molecular life sciences High 37464072
2023 MKP-1 deficiency enhances PFKFB3 expression and phosphorylation in multiple cell types during sepsis, increasing glycolysis and lactate production. Pharmacological inhibition of p38 MAPK (but not JNK) substantially attenuates PFKFB3 expression and lactate production in Mkp-1-deficient macrophages, placing p38 downstream of MKP-1 in regulation of the glycolytic program via PFKFB3. Mkp-1-/- mice; E. coli sepsis and LPS models; PFKFB3 western blotting; lactate measurement; p38 and JNK inhibitors; mRNA stability assays; multiple cell types and tissues The Journal of biological chemistry High 36803959
2024 CPT1 inhibition reduces ADP-ribosylation of DUSP1 (by decreasing PARP-1 expression), leading to decreased p38 MAPK phosphorylation and stimulation of cardiomyocyte proliferation. In cardiac-specific CPT1a/CPT1b knockout mice, cardiomyocyte proliferation and post-MI cardiac function are improved; these effects are attributed to reduced DUSP1 ADP-ribosylation and consequent p38 inactivation. Cardiac-specific Cpt1a/Cpt1b knockout mice; DUSP1 ADP-ribosylation assay; p38 MAPK phosphorylation western blotting; cardiomyocyte proliferation assay; post-MI cardiac function echocardiography; si/adRNA DUSP1 and PARP1 manipulation Acta pharmaceutica Sinica. B Medium 40041918
2016 In MKP-1-deficient macrophages, LPS-induced MKP-1 absence leads to increased p38 activity and elevated HIF-1α expression (via increased ROS and decreased prolyl hydroxylase expression), which in turn drives increased IL-1β production. p38 inhibition reduces pro-IL-1β and HIF-1α in MKP-1-deficient BMDMs. MKP-1-deficient bone marrow-derived macrophages; p38 and JNK phosphorylation assays; HIF-1α western blotting; ROS measurement; prolyl hydroxylase mRNA; IL-1β ELISA; pharmacological p38 and HIF-1α inhibitors Cellular signalling Medium 28238855
2019 Chronic stress in mice increases Mkp-1 expression in the hippocampus via glucocorticoid signaling; increased Mkp-1 debilitates p-CREB and PPARγ, which suppresses epigenetic factors HDAC2 and SUV39H1, which normally repress Mkp-1 transcription, creating a positive feedback loop. MKP-1 hippocampal overexpression is sufficient to induce depression-like behaviors and neuroinflammation; Mkp-1 knockdown in CUMS-exposed rats reverses these effects. Chronic unpredictable mild stress (CUMS) rat model; viral MKP-1 overexpression and siRNA knockdown in hippocampus; ChIP assay for HDAC2/SUV39H1 at Mkp-1 promoter; p-CREB and ERK/p38 western blotting; behavioral tests; microglial and cytokine analyses Molecular neurobiology / Translational psychiatry Medium 31267372 38424085

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1. The EMBO journal 390 11742987
1995 Inactivation of p42 MAP kinase by protein phosphatase 2A and a protein tyrosine phosphatase, but not CL100, in various cell lines. Current biology : CB 318 7780739
1993 The human CL100 gene encodes a Tyr/Thr-protein phosphatase which potently and specifically inactivates MAP kinase and suppresses its activation by oncogenic ras in Xenopus oocyte extracts. Oncogene 318 8390041
2011 p38/MKP-1-regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair. The Journal of cell biology 193 21987635
2008 MKP-1 mRNA stabilization and translational control by RNA-binding proteins HuR and NF90. Molecular and cellular biology 188 18490444
1998 Conditional expression of mitogen-activated protein kinase phosphatase-1, MKP-1, is cytoprotective against UV-induced apoptosis. Proceedings of the National Academy of Sciences of the United States of America 154 9501207
2016 Role of DUSP1/MKP1 in tumorigenesis, tumor progression and therapy. Cancer medicine 137 27227569
2010 The MAP kinase phosphatase MKP-1 regulates BDNF-induced axon branching. Nature neuroscience 129 20935641
2000 CL100/MKP-1 modulates JNK activation and apoptosis in response to cisplatin. Oncogene 125 11064451
2007 ERK-dependent MKP-1-mediated cisplatin resistance in human ovarian cancer cells. Cancer research 117 18089824
2011 Mitogen-activated protein kinase phosphatase (MKP)-1 in immunology, physiology, and disease. Life sciences 111 22197448
2013 MAP kinase phosphatase 1 (MKP-1/DUSP1) is neuroprotective in Huntington's disease via additive effects of JNK and p38 inhibition. The Journal of neuroscience : the official journal of the Society for Neuroscience 97 23392662
2002 Expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) in primary human ovarian carcinoma. International journal of cancer 94 12432554
2017 PARP inhibition protects mitochondria and reduces ROS production via PARP-1-ATF4-MKP-1-MAPK retrograde pathway. Free radical biology & medicine 90 28457938
2010 DUSP1/MKP1 promotes angiogenesis, invasion and metastasis in non-small-cell lung cancer. Oncogene 88 20890299
2019 MKP-1 reduces Aβ generation and alleviates cognitive impairments in Alzheimer's disease models. Signal transduction and targeted therapy 87 31840000
2017 Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia. Nature medicine 87 28319094
2006 MKP1/CL100 controls tumor growth and sensitivity to cisplatin in non-small-cell lung cancer. Oncogene 84 16462770
2009 MKP-1 is necessary for T cell activation and function. The Journal of biological chemistry 73 19748894
2008 Acetylation of MKP-1 and the control of inflammation. Science signaling 72 18922786
2018 DUSP1 recuses diabetic nephropathy via repressing JNK-Mff-mitochondrial fission pathways. Journal of cellular physiology 71 30191967
2006 Feedback control of MKP-1 expression by p38. Cellular signalling 68 16978838
2016 Role for DUSP1 (dual-specificity protein phosphatase 1) in the regulation of autophagy. Autophagy 67 27459239
2018 DUSP1 induces apatinib resistance by activating the MAPK pathway in gastric cancer. Oncology reports 66 29956792
2004 Role of MAPK phosphatase-1 (MKP-1) in adipocyte differentiation. The Journal of biological chemistry 65 15269202
2010 Dysregulation of p38 and MKP-1 in response to NOD1/TLR4 stimulation in sarcoid bronchoalveolar cells. American journal of respiratory and critical care medicine 61 20851927
2004 Cellular defense against H2O2-induced apoptosis via MAP kinase-MKP-1 pathway. Free radical biology & medicine 60 15059639
2018 Mkp-1 cross-talks with Nrf2/Ho-1 pathway protecting against intestinal inflammation. Free radical biology & medicine 58 30061089
2002 CAMP-dependent protein kinase enhances CYP17 transcription via MKP-1 activation in H295R human adrenocortical cells. The Journal of biological chemistry 58 12506119
2016 MicroRNA-200c modulates DUSP-1 expression in diabetes-induced cardiac hypertrophy. Molecular and cellular biochemistry 57 27696308
2019 Long noncoding RNA LINC01111 suppresses pancreatic cancer aggressiveness by regulating DUSP1 expression via microRNA-3924. Cell death & disease 56 31767833
2011 Progesterone receptor inhibits proliferation of human breast cancer cells via induction of MAPK phosphatase 1 (MKP-1/DUSP1). The Journal of biological chemistry 55 22020934
2023 DUSP1 protects against ischemic acute kidney injury through stabilizing mtDNA via interaction with JNK. Cell death & disease 54 37935658
2009 Involvement of MKP-1 and Bcl-2 in acquired cisplatin resistance in ovarian cancer cells. Cell cycle (Georgetown, Tex.) 54 19755862
2018 Geniposide regulates the miR-101/MKP-1/p38 pathway and alleviates atherosclerosis inflammatory injury in ApoE-/- mice. Immunobiology 51 30630636
2017 MKP-1 negatively regulates LPS-mediated IL-1β production through p38 activation and HIF-1α expression. Cellular signalling 49 28238855
1995 Induction of CL100 protein tyrosine phosphatase following transient forebrain ischemia in the rat brain. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 49 7798338
2002 CL100 expression is down-regulated in advanced epithelial ovarian cancer and its re-expression decreases its malignant potential. Oncogene 47 12080474
2017 Obacunone causes sustained expression of MKP-1 thus inactivating p38 MAPK to suppress pro-inflammatory mediators through intracellular MIF. Journal of cellular biochemistry 46 28657665
2011 Overexpression of Runx2 and MKP-1 stimulates transdifferentiation of 3T3-L1 preadipocytes into bone-forming osteoblasts in vitro. Calcified tissue international 46 21258786
2014 MAP kinase phosphatase DUSP1 is overexpressed in obese humans and modulated by physical exercise. American journal of physiology. Endocrinology and metabolism 45 25370852
2003 ANP inhibits TNF-alpha-induced endothelial MCP-1 expression--involvement of p38 MAPK and MKP-1. Journal of leukocyte biology 45 12960255
2019 DUSP1/MKP-1 regulates proliferation and apoptosis in keratinocytes through the ERK/Elk-1/Egr-1 signaling pathway. Life sciences 44 30858120
2023 The Ninj1/Dusp1 Axis Contributes to Liver Ischemia Reperfusion Injury by Regulating Macrophage Activation and Neutrophil Infiltration. Cellular and molecular gastroenterology and hepatology 43 36731792
2020 The p38/MKP-1 signaling axis in oral cancer: Impact of tumor-associated macrophages. Oral oncology 41 32058294
2012 Mitogen-activated protein kinase phosphatase (Mkp)-1 protects mice against acetaminophen-induced hepatic injury. Toxicologic pathology 41 22623522
2008 Elk-1, CREB, and MKP-1 regulate Egr-1 expression in gonadotropin-releasing hormone stimulated gonadotrophs. Journal of cellular biochemistry 41 18814180
2017 DUSP1 inhibits cell proliferation, metastasis and invasion and angiogenesis in gallbladder cancer. Oncotarget 40 28129656
2017 Role and regulation of MKP-1 in airway inflammation. Respiratory research 40 28797290
2015 DUSP1 expression induced by HDAC1 inhibition mediates gefitinib sensitivity in non-small cell lung cancers. Clinical cancer research : an official journal of the American Association for Cancer Research 40 25593344
2011 Over-expression of map kinase phosphatase-1 (MKP-1) suppresses neuronal death through regulating JNK signaling in hypoxia/re-oxygenation. Brain research 39 22197701
2014 Inhibition of mitogen-activated protein kinase phosphatase-1 (MKP-1) increases experimental stroke injury. Experimental neurology 38 24842488
2022 PDGF-R inhibition induces glioblastoma cell differentiation via DUSP1/p38MAPK signalling. Oncogene 37 35393545
2011 MAPK phosphatase-1 (MKP-1) expression is up-regulated by hCG/cAMP and modulates steroidogenesis in MA-10 Leydig cells. Endocrinology 37 21558315
2014 DUSP1 phosphatase regulates the proinflammatory milieu in head and neck squamous cell carcinoma. Cancer research 36 25312268
2012 Targeting mitogen-activated protein kinase phosphatase-1 (MKP-1): structure-based design of MKP-1 inhibitors and upregulators. Current medicinal chemistry 34 22320295
2009 Role of MKP-1 in osteoclasts and bone homeostasis. The American journal of pathology 34 19762714
2015 Association Between MKP-1, BDNF, and Gonadal Hormones with Depression on Perimenopausal Women. Journal of women's health (2002) 31 26176177
2014 Critical role of MKP-1 in lipopolysaccharide-induced osteoclast formation through CXCL1 and CXCL2. Cytokine 31 25261746
2021 Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4. Nature communications 30 34785669
2019 Mkp-1 is required for chemopreventive activity of butylated hydroxyanisole and resveratrol against colitis-associated colon tumorigenesis. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 30 30844440
2016 Anti-Inflammatory Effects of β2-Receptor Agonists Salbutamol and Terbutaline Are Mediated by MKP-1. PloS one 30 26849227
2023 p38 MAPK and MKP-1 control the glycolytic program via the bifunctional glycolysis regulator PFKFB3 during sepsis. The Journal of biological chemistry 29 36803959
2019 Deficit of mitogen-activated protein kinase phosphatase 1 (DUSP1) accelerates progressive hearing loss. eLife 29 30938680
2023 DUSP1 interacts with and dephosphorylates VCP to improve mitochondrial quality control against endotoxemia-induced myocardial dysfunction. Cellular and molecular life sciences : CMLS 28 37464072
2014 Mitogen-Activated Protein Kinase Phosphatase (MKP)-1 in Nervous System Development and Disease. Molecular neurobiology 28 24957007
2012 MKP-1: a critical phosphatase in the biology of macrophages controlling the switch between proliferation and activation. European journal of immunology 28 22865045
2007 Dual specificity phosphatase 1/CL100 is a direct transcriptional target of E2F-1 in the apoptotic response to oxidative stress. Cancer research 28 17638884
2020 Clostridium difficile toxin B induces colonic inflammation through the TRIM46/DUSP1/MAPKs and NF-κB signalling pathway. Artificial cells, nanomedicine, and biotechnology 27 31918570
2004 Inhibition of MKP-1 expression potentiates JNK related apoptosis in renal cancer cells. The Journal of urology 27 15247770
2004 Mitogen-activated protein kinase phosphatase-1 (MKP-1): >100-fold nocturnal and norepinephrine-induced changes in the rat pineal gland. FEBS letters 27 15527789
2024 Down-regulation of MKP-1 in hippocampus protects against stress-induced depression-like behaviors and neuroinflammation. Translational psychiatry 25 38424085
2024 piRNA PROPER Suppresses DUSP1 Translation by Targeting N6-Methyladenosine-Mediated RNA Circularization to Promote Oncogenesis of Prostate Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 25 38962952
2020 D-allose alleviates ischemia/reperfusion (I/R) injury in skin flap via MKP-1. Molecular medicine (Cambridge, Mass.) 25 32046628
2018 USP49 inhibits ischemia-reperfusion-induced cell viability suppression and apoptosis in human AC16 cardiomyocytes through DUSP1-JNK1/2 signaling. Journal of cellular physiology 25 30246457
2017 MKP-1 suppresses PARP-1 degradation to mediate cisplatin resistance. Oncogene 24 28650468
2025 Ginsenoside Rb1 attenuates coronary microvascular inflammatory injury via NDUFS4-SIRT5-DUSP1-mediated mitochondrial quality control in a murine ischemia-reperfusion model. Journal of ginseng research 23 40843019
2017 DUSP1 is involved in the progression of small cell carcinoma of the prostate. Saudi journal of biological sciences 23 30108432
1997 Differential regulation of the dual-specificity protein-tyrosine phosphatases CL100, B23, and PAC1 in mesangial cells. Journal of the American Society of Nephrology : JASN 23 9013447
2021 DUSP1 overexpression attenuates renal tubular mitochondrial dysfunction by restoring Parkin-mediated mitophagy in diabetic nephropathy. Biochemical and biophysical research communications 22 33940385
2021 Secoisolariciresinol diglucoside mitigates benzo[a]pyrene-induced liver and kidney toxicity in mice via miR-101a/MKP-1-mediated p38 and ERK pathway. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 22 34856318
2012 MKP-1 coordinates ordered macrophage-phenotype transitions essential for stem cell-dependent tissue repair. Cell cycle (Georgetown, Tex.) 22 22361726
2010 Mitogen-activated protein kinase phosphatase-1 (MKP-1) in retinal ischemic preconditioning. Experimental eye research 22 21094639
2008 Protecting the stress response, guarding the MKP-1 mRNA. Cell cycle (Georgetown, Tex.) 22 18728392
2008 Pancreatic reg I binds MKP-1 and regulates cyclin D in pancreatic-derived cells. The Journal of surgical research 22 18929742
2008 The MAP kinase phosphatase-1 MKP-1/DUSP1 is a regulator of human liver response to transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 22 19032224
2004 MKP-1 expression and stabilization and cGK Ialpha prevent diabetes- associated abnormalities in VSMC migration. American journal of physiology. Cell physiology 22 15355857
2019 Stress-Induced Epigenetic Changes in Hippocampal Mkp-1 Promote Persistent Depressive Behaviors. Molecular neurobiology 21 31267372
2016 DUSP1 Maintains IRF1 and Leads to Increased Expression of IRF1-dependent Genes: A MECHANISM PROMOTING GLUCOCORTICOID INSENSITIVITY. The Journal of biological chemistry 21 27551049
1994 The CL100 gene, which encodes a dual specificity (Tyr/Thr) MAP kinase phosphatase, is highly conserved and maps to human chromosome 5q34. Human genetics 21 8168826
2025 A novel ligustrazine-based nanodelivery system protects against doxorubicin-induced cardiotoxicity by targeting the SIRT5-DUSP1 axis for mitochondrial repair. Journal of nanobiotechnology 20 41088207
2018 MKP-1 promotes anti-inflammatory M(IL-4/IL-13) macrophage phenotype and mediates the anti-inflammatory effects of glucocorticoids. Basic & clinical pharmacology & toxicology 20 30388313
2017 Mkp-1 protects mice against toxin-induced liver damage by promoting the Nrf2 cytoprotective response. Free radical biology & medicine 20 29241671
2000 Glucagon-induced expression of the MAP kinase phosphatase MKP-1 in rat hepatocytes. Gastroenterology 20 10784592
2018 Puerarin promotes DUSP1 expression by regulating miR‑133a‑3p in breast cancer. Molecular medicine reports 19 30483784
2024 Reversing metabolic reprogramming by CPT1 inhibition with etomoxir promotes cardiomyocyte proliferation and heart regeneration via DUSP1 ADP-ribosylation-mediated p38 MAPK phosphorylation. Acta pharmaceutica Sinica. B 18 40041918
2022 STAMBPL1 promotes breast cancer cell resistance to cisplatin partially by stabilizing MKP-1 expression. Oncogene 18 35236965
2022 Edaravone Dexborneol Alleviates Cerebral Ischemic Injury via MKP-1-Mediated Inhibition of MAPKs and Activation of Nrf2. BioMed research international 18 36110124
2013 Licorice-derived dehydroglyasperin C increases MKP-1 expression and suppresses inflammation-mediated neurodegeneration. Neurochemistry international 18 24083986
2010 Exercise training upregulates macrophage MKP-1 and affects immune responses in mice. Medicine and science in sports and exercise 18 20404768

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