Affinage

DUSP1

Dual specificity protein phosphatase 1 · UniProt P28562

Length
367 aa
Mass
39.3 kDa
Annotated
2026-04-28
100 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DUSP1 (MKP-1) is a nuclear dual-specificity phosphatase that serves as a central negative-feedback regulator of MAPK signaling, directly dephosphorylating and inactivating p38, JNK, and ERK to terminate inflammatory, stress, and mitogenic cascades across diverse cell types (PMID:16380512, PMID:11139479, PMID:17404316). Its substrate selectivity and activity are modulated by TLR-induced lysine acetylation that enhances p38 binding (PMID:18922786), by PARP1-mediated ADP-ribosylation (PMID:40041918), and by ERK2-dependent phosphorylation at Ser296/Ser323 that triggers SCF(Skp2)-mediated proteasomal degradation, creating a positive feedback loop sustaining ERK activation (PMID:16286470); protein stability is additionally controlled by USP49-mediated deubiquitination and TRIM55-mediated ubiquitination (PMID:30246457, PMID:32463795). By restraining p38 and JNK in macrophages, DUSP1 limits inflammatory cytokine production, controls macrophage polarization during tissue repair via a p38–miR-21–PTEN–Akt axis, and regulates sepsis-associated glycolytic reprogramming through p38-dependent PFKFB3 expression (PMID:16380512, PMID:21987635, PMID:36803959). Beyond immunity, DUSP1-mediated JNK dephosphorylation promotes BDNF-induced axon branching by stabilizing microtubules (PMID:20935641), preserves mitochondrial integrity by preventing BAX translocation and by dephosphorylating VCP at Ser784 to support mitochondrial quality control (PMID:37935658, PMID:37464072), and suppresses autophagy through ERK-dependent ULK1/BECN1 phosphorylation (PMID:27459239).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2001 High

    Establishing DUSP1 as a broad MAPK phosphatase: overexpression and transgenic studies demonstrated that MKP-1 directly dephosphorylates p38, JNK, and ERK in cardiomyocytes and that this activity is sufficient to block cardiac hypertrophy, placing DUSP1 as a functional antagonist of all three major MAPK branches in vivo.

    Evidence Adenovirus-mediated overexpression in primary cardiomyocytes plus cardiac-specific transgenic mice with aortic banding

    PMID:11139479

    Open questions at the time
    • substrate preference hierarchy not resolved
    • catalytic mechanism and structural basis for dual specificity not determined
  2. 2004 Medium

    Defining DUSP1 as a physiological regulator of differentiation through ERK inactivation: MKP-1 upregulation during adipogenesis was shown to be required for ERK shutoff and adipocyte differentiation, demonstrating a developmental role beyond stress signaling.

    Evidence Antisense knockdown and overexpression in 3T3-L1 preadipocytes with MEK inhibitor rescue

    PMID:15269202

    Open questions at the time
    • transcriptional mechanism driving MKP-1 upregulation during differentiation not identified
    • relevance to in vivo adipose development untested
  3. 2005 High

    Resolving the in vivo substrate selectivity and physiological importance of DUSP1 in innate immunity: Dusp1-knockout mice revealed that DUSP1 preferentially restrains p38 (not ERK) in LPS-stimulated macrophages, limiting cytokine production and preventing lethal endotoxic shock.

    Evidence Dusp1−/− mice and bone marrow-derived macrophages challenged with LPS, transcriptional profiling

    PMID:16380512

    Open questions at the time
    • relative contribution of JNK dephosphorylation in the same system remained unclear
    • redundancy with other DUSPs not addressed
  4. 2005 High

    Discovering ERK-driven proteolytic turnover of DUSP1 via SCF(Skp2): ERK2 phosphorylation of MKP-1 at Ser296/Ser323 through its DEF motif was shown to trigger SCF(Skp2)-mediated ubiquitination and degradation, establishing a positive feedback loop that sustains ERK signaling.

    Evidence In vitro kinase assays, site-directed mutagenesis of DEF motif and Ser296/Ser323, reciprocal Co-IP with Skp2, Skp2 siRNA

    PMID:16286470

    Open questions at the time
    • ubiquitination sites on MKP-1 not mapped
    • kinetics of this feedback loop in vivo not measured
  5. 2006 Medium

    Identifying a p38→MK2→MKP-1 negative feedback loop: p38-dependent, MK2-mediated post-transcriptional stabilization of MKP-1 mRNA was shown to limit MAPK activation and underlie endotoxin tolerance in macrophages.

    Evidence p38 inhibitor, MK2 RNAi, cycloheximide chase in macrophages

    PMID:16978838

    Open questions at the time
    • specific mRNA stability elements in MKP-1 3′UTR not identified
    • MK2 phosphorylation target mediating mRNA stabilization unknown
  6. 2007 High

    Extending DUSP1's innate immune role to Gram-positive stimuli and confirming JNK as a co-substrate: Mkp-1−/− macrophages stimulated with peptidoglycan and lipoteichoic acid showed prolonged p38 and JNK (but not ERK) activation, broadening substrate selectivity beyond p38 alone.

    Evidence Mkp-1 KO macrophages stimulated with PGN/LTA, phospho-MAPK blotting, cytokine measurement

    PMID:17404316

    Open questions at the time
    • whether stimulus-specific substrate selectivity reflects differential DUSP1 PTMs not tested
  7. 2007 Medium

    Identifying E2F-1 as a direct transcriptional activator of DUSP1 linking cell cycle regulators to MAPK termination: ChIP showed E2F-1 binds the DUSP1 promoter and induces DUSP1-mediated ERK dephosphorylation during oxidative stress-induced apoptosis.

    Evidence ChIP, promoter-luciferase reporter, E2F-1 overexpression, ERK dephosphorylation assay

    PMID:17638884

    Open questions at the time
    • whether endogenous E2F-1 loss phenocopies DUSP1 deficiency not tested
    • other E2F family members not examined
  8. 2008 Medium

    Revealing acetylation as a regulatory switch for DUSP1 substrate engagement: TLR-induced lysine acetylation of MKP-1 was found to promote its physical interaction with p38, providing a post-translational mechanism that enhances phosphatase–substrate coupling.

    Evidence PTM analysis and protein–protein interaction assay in TLR-stimulated cells

    PMID:18922786

    Open questions at the time
    • specific acetyltransferase and acetylated lysine residue identity not firmly established in this entry
    • whether acetylation alters JNK or ERK binding unknown
  9. 2010 High

    Establishing a neuronal function for DUSP1 in axon branching: BDNF-induced MKP-1 expression was shown to dephosphorylate JNK, thereby stabilizing microtubules and enabling axon branch formation; mkp-1-null neurons were unable to branch in response to BDNF.

    Evidence mkp-1 KO neurons, BDNF stimulation, live imaging of axon branching

    PMID:20935641

    Open questions at the time
    • specific JNK substrates on microtubules (e.g., SCG10, DCX) responsible for branch suppression not identified
    • in vivo brain connectivity phenotype not fully characterized
  10. 2011 High

    Defining DUSP1's role in macrophage polarization and tissue repair: MKP-1 loss was shown to drive sustained p38 activity, inducing miR-21 which reduces PTEN and extends Akt activation, disrupting the macrophage pro- to anti-inflammatory transition required for skeletal muscle healing.

    Evidence MKP-1-deficient mice, skeletal muscle injury, pharmacological p38 inhibition, miR-21/PTEN/Akt analysis

    PMID:21987635

    Open questions at the time
    • whether this polarization mechanism operates in other tissues not tested
    • direct p38 target driving miR-21 transcription unknown
  11. 2015 Medium

    Linking adrenergic stress signaling to DUSP1-mediated chemoresistance: norepinephrine/ADRB2 signaling through cAMP–PKC–CREB was found to induce DUSP1, which inactivates JNK and suppresses c-Jun-mediated apoptosis, protecting ovarian cancer cells from paclitaxel and cisplatin.

    Evidence Norepinephrine treatment, ADRB2 pathway dissection, DUSP1 overexpression/silencing, in vivo chronic stress model

    PMID:26581245

    Open questions at the time
    • CREB binding site in DUSP1 promoter not mapped by ChIP
    • generalizability across cancer types unclear
  12. 2016 Medium

    Discovering DUSP1 as a suppressor of autophagy through ERK-ULK1/BECN1 signaling: DUSP1 loss activated ERK-dependent phosphorylation of ULK1(Ser555) and BECN1(Ser15), promoting VPS34 complex assembly and autophagosome initiation.

    Evidence shRNA/genetic KO in MEFs and ovarian cancer cells, Co-IP of VPS34-ATG14-BECN1-MAPK complex, pharmacological inhibitor epistasis

    PMID:27459239

    Open questions at the time
    • whether DUSP1 directly dephosphorylates ULK1/BECN1 or acts solely through ERK not resolved
    • physiological context of DUSP1-autophagy axis in vivo not tested
  13. 2018 Medium

    Identifying ubiquitin-mediated stabilization of DUSP1 by USP49: USP49 was shown to directly deubiquitinate DUSP1, stabilizing it and thereby suppressing JNK phosphorylation and cardiomyocyte apoptosis in ischemia-reperfusion injury.

    Evidence Reciprocal Co-IP, ubiquitination assay, USP49 overexpression/knockdown in cardiomyocytes and rat I/R model

    PMID:30246457

    Open questions at the time
    • ubiquitination sites on DUSP1 targeted by USP49 not mapped
    • relationship between USP49 and SCF(Skp2)-mediated degradation not addressed
  14. 2018 High

    Demonstrating DUSP1's metabolic role in skeletal muscle: muscle-specific MKP-1 deletion increased p38/JNK activity, enhanced energy expenditure and mitochondrial respiration, and activated the miR-21–PTEN–Akt axis to improve insulin sensitivity, protecting against diet-induced obesity.

    Evidence Muscle-specific MKP-1 KO mice, high-fat diet, indirect calorimetry, mitochondrial respiration, miR-21/PTEN/Akt analysis

    PMID:29317435

    Open questions at the time
    • direct transcriptional targets of p38/JNK driving mitochondrial biogenesis in muscle not identified
    • whether macrophage-intrinsic effects contribute to the metabolic phenotype not excluded
  15. 2020 Medium

    Identifying TRIM55 as an E3 ligase for DUSP1 degradation: TRIM55 was shown to ubiquitinate DUSP1, promoting its degradation and JNK activation in cardiomyocyte ischemia-reperfusion, with miR-378a-3p restraining TRIM55 levels.

    Evidence TRIM55 overexpression/knockdown, ubiquitination assay, miR-378a-3p luciferase reporter, rat I/R model

    PMID:32463795

    Open questions at the time
    • TRIM55 ubiquitination sites on DUSP1 not mapped
    • interplay between SCF(Skp2)- and TRIM55-mediated degradation not examined
  16. 2023 High

    Revealing DUSP1 as a guardian of mitochondrial integrity via JNK–BAX and VCP dephosphorylation: DUSP1 deficiency was shown to cause aberrant JNK-mediated BAX mitochondrial translocation and mtDNA leakage activating cGAS-STING, while DUSP1 also directly dephosphorylates VCP at Ser784 to support mitochondrial quality control during endotoxemia.

    Evidence Dusp1 KO mice, tubular STING KO epistasis, Co-IP of DUSP1-JNK and DUSP1-VCP, phosphomimetic VCP(S784D) mutant, DUSP1 transgenic mice

    PMID:37464072 PMID:37935658

    Open questions at the time
    • whether VCP Ser784 dephosphorylation occurs in non-cardiac tissues not tested
    • structural basis for DUSP1 recognizing VCP versus canonical MAPK substrates unknown
  17. 2023 Medium

    Connecting DUSP1 to metabolic reprogramming in sepsis: the p38–PFKFB3–glycolysis axis was shown to be restrained by MKP-1; Mkp-1-deficient mice had elevated PFKFB3 and lactate during E. coli infection, demonstrating DUSP1 as a metabolic checkpoint in inflammation.

    Evidence Mkp-1 KO mice, E. coli infection, PFKFB3 expression and lactate measurements, p38/JNK inhibitor epistasis

    PMID:36803959

    Open questions at the time
    • whether DUSP1 directly regulates PFKFB3 phosphorylation or acts only via p38 not distinguished
    • relevance to human sepsis not established
  18. 2024 Medium

    Identifying ADP-ribosylation as a novel regulatory modification of DUSP1: CPT1 inhibition reduced PARP1 expression and DUSP1 ADP-ribosylation, decreasing p38 phosphorylation and promoting cardiomyocyte proliferation, establishing a metabolic–epigenetic–MAPK axis in heart regeneration.

    Evidence Cardiac-specific Cpt1a/Cpt1b KO mice, DUSP1 ADP-ribosylation assay, myocardial infarction model

    PMID:40041918

    Open questions at the time
    • specific ADP-ribosylation site(s) on DUSP1 not mapped
    • whether ADP-ribosylation affects DUSP1 catalytic activity or stability not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for DUSP1's discrimination among MAPK substrates versus non-MAPK substrates like VCP, the full catalog and functional consequences of DUSP1 post-translational modifications (acetylation sites, ADP-ribosylation sites, phosphodegron regulation in different tissues), and the extent of functional redundancy with other nuclear DUSPs in vivo.
  • no crystal structure of DUSP1 in complex with any substrate
  • functional redundancy with DUSP2/DUSP4/DUSP5 not systematically tested
  • tissue-specific PTM code governing substrate selectivity uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0098772 molecular function regulator activity 5
Localization
GO:0005634 nucleus 3 GO:0005739 mitochondrion 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-168256 Immune System 6 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1430728 Metabolism 2 R-HSA-9612973 Autophagy 1
Partners
EZH2MAPK1MAPK14MAPK8SKP2TRIM55USP49VCP

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 DUSP1/MKP-1 selectively dephosphorylates and inactivates p38 MAPK (but not ERK) in macrophages following LPS stimulation, thereby limiting inflammatory cytokine production (IL-6, TNF-α, IL-10, CCL3, CCL4, CXCL2); DUSP1-deficient macrophages show prolonged p38 activation and Dusp1-/- mice exhibit lethal endotoxin shock. Genetic knockout (Dusp1-/- mice), bone marrow-derived macrophage assays, transcriptional profiling, LPS challenge model The Journal of experimental medicine High 16380512
2001 MKP-1 directly dephosphorylates and inactivates p38, JNK1/2, and ERK1/2 in cardiomyocytes; adenovirus-mediated MKP-1 expression blocked agonist-induced hypertrophy in vitro, and cardiac-specific MKP-1 transgenic mice showed attenuated developmental and pressure-overload hypertrophy. Adenovirus-mediated gene transfer in primary cardiomyocytes, cardiac-specific transgenic mice, aortic banding model Circulation research High 11139479
2010 BDNF signaling induces MKP-1 expression, which causes spatiotemporal deactivation of JNK, reducing phosphorylation of JNK substrates that destabilize microtubules, thereby promoting axon branching; mkp-1 null neurons cannot produce axon branches in response to BDNF. mkp-1 null mouse neurons, BDNF stimulation assays, live imaging of axon branching Nature neuroscience High 20935641
2005 Active ERK2 docks to the DEF motif (FXFP, residues 339–342) of MKP-1 and phosphorylates it at Ser296/Ser323, triggering ubiquitin-mediated MKP-1 proteolysis via the SCF(Skp2) E3 ubiquitin ligase, thereby creating a positive feedback loop that sustains ERK activation. In vitro kinase assay with N-terminally truncated MKP-1, site-directed mutagenesis (DEF motif, Ser296/Ser323, Ser359/Ser364), Co-IP of phospho-Ser296 MKP-1 with SCF(Skp2) in vivo and in vitro, siRNA depletion of Skp2 The Journal of biological chemistry High 16286470
2007 ERK2 phosphorylates MKP-1 in cisplatin-treated ovarian cancer cells; ERK2-mediated MKP-1 phosphorylation stabilizes MKP-1 and promotes cisplatin resistance by maintaining Bcl-2 levels; inhibition of ERK2 (by U0126 or siRNA) decreases MKP-1 induction and sensitizes cells to cisplatin. MEK1/2 inhibitor (U0126), siRNA silencing of ERK2, Western blotting for phospho-MKP-1, cisplatin-induced apoptosis assays in human ovarian cancer cell lines Cancer research Medium 18089824
2011 MKP-1 restricts p38 MAPK activation during muscle repair; loss of MKP-1 leads to p38-induced miR-21 expression, which reduces PTEN levels, thereby extending AKT activation and disrupting the macrophage pro- to anti-inflammatory transition needed for tissue healing. MKP-1-deficient mice, skeletal muscle injury model, pharmacological p38 inhibition, miR-21/PTEN/AKT pathway analysis The Journal of cell biology High 21987635
2008 MKP-1 is acetylated on a key lysine residue following TLR stimulation; this acetylation promotes the interaction of MKP-1 with its substrate p38 MAPK, resulting in p38 dephosphorylation and attenuation of innate immune responses. Post-translational modification analysis, protein–protein interaction assay (MKP-1 acetylation promoting MKP-1–p38 interaction) Science signaling Medium 18922786
2006 p38 MAPK promotes MKP-1 expression at a post-transcriptional level (not mRNA level) in LPS/PGN-stimulated macrophages; this effect is mediated by the downstream kinase MK2 (MAPKAP kinase 2), establishing a p38→MK2→MKP-1 feedback loop that limits MAPK activation and mediates endotoxin tolerance. p38 inhibitor (SB203580), RNAi knockdown of p38 and MK2, Northern blotting, cycloheximide chase in macrophages Cellular signalling Medium 16978838
2005 Heat shock regulates MKP-1 gene expression through both transcriptional (HSF-1-independent; requires two putative heat shock elements in the MKP-1 promoter) and post-transcriptional (increased mRNA stability, dependent on p38 MAPK activity) mechanisms. HSF-1-null fibroblasts, site-directed mutagenesis of MKP-1 promoter, MKP-1 promoter luciferase reporter, mRNA stability assay, p38 inhibitor (SB203580) American journal of physiology. Cell physiology Medium 15958526
2004 MKP-1 abundance increases during adipocyte differentiation and is responsible for down-regulating p42/p44 MAPK activity; antisense-mediated prevention of MKP-1 up-regulation sustained MAPK activation and blocked differentiation, effects reversed by the MEK inhibitor PD98059. MKP-1 antisense RNA expression in 3T3-L1 preadipocytes, ectopic MKP-1 overexpression, MEK inhibitor PD98059, MAPK activity assays The Journal of biological chemistry Medium 15269202
2007 MKP-1 (DUSP1) dephosphorylates p38 MAPK and JNK in macrophages following stimulation with Gram-positive bacterial cell wall components (peptidoglycan, lipoteichoic acid); Mkp-1-/- macrophages show prolonged p38 and JNK (but not ERK) activation and increased TNF-α and IL-6 production. Mkp-1 knockout mice, macrophage stimulation with PGN and LTA, phospho-MAPK Western blotting, cytokine measurement Journal of immunology High 17404316
2009 MKP-1 promotes cisplatin resistance in ovarian cancer by maintaining PARP-1 protein levels; MKP-1 suppresses JNK1/2 activity, which prevents PARP-1 ubiquitination and degradation; silencing MKP-1 increases JNK-mediated PARP-1 ubiquitination and reduces PARP-1 protein levels, sensitizing cells to cisplatin. MKP-1 siRNA silencing, JNK1/2 siRNA, ubiquitination assay, PARP-1/PAR Western blotting, cisplatin sensitivity assays in ovarian cancer cells Oncogene Medium 28650468
2016 DUSP1 knockdown increases autophagic flux in ovarian cancer cells and murine embryonic fibroblasts; DUSP1 knockout promotes phosphorylation of ULK1 (Ser555) and BECN1 (Ser15) and assembly of the PIK3C3/VPS34-ATG14-BECN1-MAPK complex activating the autophagosome-initiating PtdIns3K complex; DUSP1-mediated autophagy suppression operates through inactivation of MAPK1/MAPK3 (ERK). shRNA knockdown and genetic knockout (MEFs), rapamycin-induced autophagy assay, phosphorylation analysis of ULK1 and BECN1, complex co-immunoprecipitation, pharmacological inhibitor studies Autophagy Medium 27459239
2007 E2F-1 is a direct transcriptional activator of DUSP1; E2F-1 binds to an E2F-1 consensus sequence and palindromic motif in the DUSP1 promoter (shown by ChIP and promoter-luciferase assay), induces DUSP1 expression upon oxidative stress, and uses DUSP1 to dephosphorylate ERK1/2 in the apoptotic response to oxidative stress. ChIP assay, DUSP1 promoter-luciferase reporter, ectopic E2F-1 expression, ERK1/2 dephosphorylation assay Cancer research Medium 17638884
2009 MKP-1 negatively regulates RANKL-induced p38 MAPK and JNK activities in osteoclasts; mkp-1-/- female mice have slightly reduced bone mass, and mkp-1-/- osteoclasts have enhanced resorptive activity; RANKL induces MKP-1 expression in osteoclasts. mkp-1 knockout mice, ovariectomy model, local LPS injection, RANKL-stimulated osteoclast cultures, p38/JNK activity assays The American journal of pathology Medium 19762714
2023 DUSP1 directly binds JNK and dephosphorylates it; DUSP1 deficiency causes aberrant JNK phosphorylation and BAX mitochondrial translocation, promoting mtDNA leakage and cGAS-STING pathway activation in ischemic acute kidney injury; JNK inhibition or BAX inhibition prevents mtDNA leakage, and STING knockout mitigates the adverse effects of DUSP1 deficiency. Constitutional Dusp1 knockout mice, tubular-specific STING KO mice, co-immunoprecipitation (DUSP1-JNK direct binding), electron microscopy, mitochondrial membrane potential, BAX translocation, cGAS-STING pathway analysis Cell death & disease High 37935658
2023 DUSP1 directly interacts with and dephosphorylates valosin-containing protein (VCP) at Ser784 on the mitochondria; DUSP1 phosphatase domain mediates the DUSP1–VCP interaction; a phosphomimetic VCP (S784D) mutant abolishes DUSP1-mediated mitochondrial quality control protection during LPS-induced endotoxemia. Co-immunoprecipitation, DUSP1 transgenic mice, phosphomimetic VCP mutant transfection, mitochondrial dynamics/mitophagy/biogenesis assays in HL-1 cardiomyocytes Cellular and molecular life sciences High 37464072
2015 DUSP1 inhibits p38 MAPK phosphorylation, thereby suppressing HSP27 activation; this reduces HSP27-mediated p53 sequestration, resulting in enhanced p53 phosphorylation at S15, S20, S46 and transcriptional activation of p21 and p27 (cell cycle arrest and apoptosis); conversely, wild-type p53 transcriptionally upregulates DUSP1 via its DNA-binding domain, forming a positive regulatory loop. DUSP1 overexpression/knockdown in HCC cells, phospho-p38/HSP27/p53 Western blotting, p53 promoter binding assay, xenograft mouse model Journal of hepatology Medium 25617504
2018 Skeletal muscle-specific deletion of MKP-1 increases p38 MAPK and JNK activities, protects mice from high-fat diet-induced obesity by increasing whole-body energy expenditure and mitochondrial oxygen consumption; in MKP-1-deleted muscle, miR-21 is upregulated, reducing PTEN and increasing Akt activity, conferring enhanced insulin sensitivity. Muscle-specific MKP-1 knockout mice (MKP1-MKO), high-fat diet, indirect calorimetry, mitochondrial oxygen consumption, miR-21/PTEN/Akt pathway analysis Diabetes High 29317435
2012 MKP-1 controls the switch between macrophage proliferation and activation: growth factors induce transient ERK phosphorylation enabling proliferation, while LPS induces extended ERK phosphorylation enabling activation; MKP-1 is induced in both contexts but with different kinetics; IFN-γ inhibits MKP-1 to block proliferation and promote activation. Mouse macrophage cultures, growth factor and LPS stimulation, ERK phosphorylation kinetics, IFN-γ co-stimulation experiments European journal of immunology Medium 22865045
2013 DUSP1 expression is upregulated by vaccinia virus (VACV) infection dependent on early viral gene expression; in DUSP1-deficient cells, JNK and ERK are hyperactivated and VACV replication is enhanced; DUSP1 is involved at the stage of IVN-to-mature virion transition in VACV morphogenesis. DUSP1 KO cells and mice, viral infection assays, phospho-JNK/ERK analysis, confocal and electron microscopy of viral morphogenesis stages PLoS pathogens Medium 24244156
2008 Pancreatic Reg I protein physically binds MKP-1 (shown by yeast two-hybrid and confirmed by co-immunoprecipitation); intracellular over-expression of Reg I leads to MKP-1 inactivation and decreased cell growth. Yeast two-hybrid assay, co-immunoprecipitation, Reg I expression vector transfection The Journal of surgical research Low 18929742
2018 USP49 (ubiquitin-specific peptidase 49) directly interacts with DUSP1 and deubiquitinates it, thereby stabilizing DUSP1 protein; USP49-mediated DUSP1 stabilization suppresses JNK1/2 phosphorylation and cardiomyocyte apoptosis following ischemia-reperfusion injury. Co-immunoprecipitation of USP49 and DUSP1, ubiquitination assay, USP49 overexpression/knockdown in AC16 cardiomyocytes and rat I/R model Journal of cellular physiology Medium 30246457
2020 TRIM55 ubiquitinates DUSP1, leading to its degradation and increased JNK1/2 phosphorylation and cardiomyocyte apoptosis following ischemia-reperfusion; miR-378a-3p targets TRIM55, reducing TRIM55-mediated DUSP1 ubiquitination and thus maintaining DUSP1 levels to suppress JNK1/2. TRIM55 overexpression/knockdown, DUSP1 ubiquitination assay, luciferase reporter for miR-378a-3p targeting TRIM55, H9C2 cardiomyocyte I/R model, rat I/R model Aging Medium 32463795
2020 CASC9 lncRNA recruits histone methyltransferase EZH2 to the DUSP1 locus to epigenetically repress DUSP1 transcription; loss of DUSP1 expression activates the ERK MAPK pathway, contributing to gefitinib resistance in NSCLC. CASC9 gain/loss-of-function, EZH2 recruitment assay, DUSP1 expression rescue experiments, ERK pathway analysis in NSCLC cells and xenografts Cell death & disease Medium 33056982
2016 DUSP1 overexpression in A549 pulmonary cells maintains IRF1 expression (by switching off MAPKs that promote IRF1 mRNA and protein turnover), leading to sustained IRF1-dependent gene expression (e.g., CXCL10) that is insensitive to glucocorticoid repression; dexamethasone-induced DUSP1 thus paradoxically maintains expression of a subset of IRF1-dependent inflammatory genes. DUSP1 overexpression and siRNA silencing in A549 cells, IL-1β stimulation, MAPK inhibitors, IRF1 ChIP at target gene promoters, primary human bronchial epithelial cells The Journal of biological chemistry Medium 27551049
2024 CPT1 inhibition decreases poly(ADP-ribose) polymerase 1 (PARP1) expression, which reduces ADP-ribosylation of DUSP1; reduced DUSP1 ADP-ribosylation decreases p38 MAPK phosphorylation and promotes cardiomyocyte proliferation and heart regeneration. Cardiac-specific Cpt1a/Cpt1b knockout mice, etomoxir pharmacological inhibition, DUSP1 ADP-ribosylation assay, p38 phosphorylation analysis, myocardial infarction model Acta pharmaceutica sinica. B Medium 40041918
2015 Adrenergic stimulation (norepinephrine) via ADRB2 receptor activates cAMP-PLC-PKC-CREB signaling to induce DUSP1 expression in ovarian cancer cells; DUSP1 then inactivates JNK, reducing JNK-mediated c-Jun phosphorylation and protecting cancer cells from paclitaxel/cisplatin-induced apoptosis. Norepinephrine treatment, ADRB2 signaling pathway analysis, DUSP1 overexpression/silencing, JNK phosphorylation and apoptosis assays, in vivo chronic stress model Clinical cancer research Medium 26581245
2023 p38 MAPK and MKP-1 regulate glycolysis by controlling expression and phosphorylation of PFKFB3 during sepsis; Mkp-1-deficient mice show enhanced PFKFB3 expression and lactate production following E. coli infection or LPS stimulation; pharmacological p38 (but not JNK) inhibition attenuates PFKFB3 expression and lactate production. Mkp-1 knockout mice, E. coli infection and LPS stimulation, PFKFB3 expression analysis in multiple tissues, PFKFB3 inhibitor, p38/JNK inhibitors, lactate measurements in macrophages The Journal of biological chemistry Medium 36803959

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Dual specificity phosphatase 1 (DUSP1) regulates a subset of LPS-induced genes and protects mice from lethal endotoxin shock. The Journal of experimental medicine 274 16380512
2011 p38/MKP-1-regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair. The Journal of cell biology 192 21987635
2016 Role of DUSP1/MKP1 in tumorigenesis, tumor progression and therapy. Cancer medicine 137 27227569
2001 The dual-specificity phosphatase MKP-1 limits the cardiac hypertrophic response in vitro and in vivo. Circulation research 131 11139479
2010 The MAP kinase phosphatase MKP-1 regulates BDNF-induced axon branching. Nature neuroscience 129 20935641
2007 ERK-dependent MKP-1-mediated cisplatin resistance in human ovarian cancer cells. Cancer research 117 18089824
2005 Cooperation of ERK and SCFSkp2 for MKP-1 destruction provides a positive feedback regulation of proliferating signaling. The Journal of biological chemistry 117 16286470
1998 Increased MAPK activity and MKP-1 overexpression in human gastric adenocarcinoma. Biochemical and biophysical research communications 93 9735328
2020 Long non-coding RNA CASC9 promotes gefitinib resistance in NSCLC by epigenetic repression of DUSP1. Cell death & disease 88 33056982
2010 DUSP1/MKP1 promotes angiogenesis, invasion and metastasis in non-small-cell lung cancer. Oncogene 87 20890299
2019 MKP-1 reduces Aβ generation and alleviates cognitive impairments in Alzheimer's disease models. Signal transduction and targeted therapy 85 31840000
2017 Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia. Nature medicine 85 28319094
2007 Knockout of Mkp-1 enhances the host inflammatory responses to gram-positive bacteria. Journal of immunology (Baltimore, Md. : 1950) 84 17404316
2006 MKP1/CL100 controls tumor growth and sensitivity to cisplatin in non-small-cell lung cancer. Oncogene 84 16462770
2015 Adrenergic Stimulation of DUSP1 Impairs Chemotherapy Response in Ovarian Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 79 26581245
2008 Acetylation of MKP-1 and the control of inflammation. Science signaling 72 18922786
2018 Skeletal Muscle-Specific Deletion of MKP-1 Reveals a p38 MAPK/JNK/Akt Signaling Node That Regulates Obesity-Induced Insulin Resistance. Diabetes 69 29317435
2014 Genkwanin inhibits proinflammatory mediators mainly through the regulation of miR-101/MKP-1/MAPK pathway in LPS-activated macrophages. PloS one 69 24800851
2006 Feedback control of MKP-1 expression by p38. Cellular signalling 68 16978838
2018 DUSP1 induces apatinib resistance by activating the MAPK pathway in gastric cancer. Oncology reports 66 29956792
2016 Role for DUSP1 (dual-specificity protein phosphatase 1) in the regulation of autophagy. Autophagy 66 27459239
2019 Targeted Inhibition of the Dual Specificity Phosphatases DUSP1 and DUSP6 Suppress MPNST Growth via JNK. Clinical cancer research : an official journal of the American Association for Cancer Research 65 30936125
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
2016 MicroRNA-200c modulates DUSP-1 expression in diabetes-induced cardiac hypertrophy. Molecular and cellular biochemistry 57 27696308
2014 DUSP1 is a novel target for enhancing pancreatic cancer cell sensitivity to gemcitabine. PloS one 57 24409315
2019 Long noncoding RNA LINC01111 suppresses pancreatic cancer aggressiveness by regulating DUSP1 expression via microRNA-3924. Cell death & disease 55 31767833
2009 Involvement of MKP-1 and Bcl-2 in acquired cisplatin resistance in ovarian cancer cells. Cell cycle (Georgetown, Tex.) 54 19755862
2005 Contribution of MKP-1 regulation of p38 to endotoxin tolerance. Shock (Augusta, Ga.) 53 15614136
2020 Selenium deficiency causes immune damage by activating the DUSP1/NF-κB pathway and endoplasmic reticulum stress in chicken spleen. Food & function 52 32618989
2008 Dexamethasone reduced invasiveness of human malignant glioblastoma cells through a MAPK phosphatase-1 (MKP-1) dependent mechanism. European journal of pharmacology 49 18652821
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
2023 DUSP1 protects against ischemic acute kidney injury through stabilizing mtDNA via interaction with JNK. Cell death & disease 48 37935658
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
2010 Increased inflammation and lethality of Dusp1-/- mice in polymicrobial peritonitis models. Immunology 46 20561086
2014 Valproic acid suppresses lipopolysaccharide-induced cyclooxygenase-2 expression via MKP-1 in murine brain microvascular endothelial cells. Biochemical pharmacology 43 24552656
2014 MAP kinase phosphatase DUSP1 is overexpressed in obese humans and modulated by physical exercise. American journal of physiology. Endocrinology and metabolism 43 25370852
2021 Siglec-15 Promotes Tumor Progression in Osteosarcoma via DUSP1/MAPK Pathway. Frontiers in oncology 42 34336699
2020 The p38/MKP-1 signaling axis in oral cancer: Impact of tumor-associated macrophages. Oral oncology 41 32058294
2017 Role and regulation of MKP-1 in airway inflammation. Respiratory research 40 28797290
2015 Disruption of a regulatory loop between DUSP1 and p53 contributes to hepatocellular carcinoma development and progression. Journal of hepatology 40 25617504
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 39 25593344
2023 The Ninj1/Dusp1 Axis Contributes to Liver Ischemia Reperfusion Injury by Regulating Macrophage Activation and Neutrophil Infiltration. Cellular and molecular gastroenterology and hepatology 38 36731792
2021 Inhibition of miR‑101‑3p protects against sepsis‑induced myocardial injury by inhibiting MAPK and NF‑κB pathway activation via the upregulation of DUSP1. International journal of molecular medicine 37 33448324
2019 LncRNA GAS5 suppresses inflammatory responses and apoptosis of alveolar epithelial cells by targeting miR-429/DUSP1. Experimental and molecular pathology 37 31837322
2022 PDGF-R inhibition induces glioblastoma cell differentiation via DUSP1/p38MAPK signalling. Oncogene 36 35393545
2014 DUSP1 phosphatase regulates the proinflammatory milieu in head and neck squamous cell carcinoma. Cancer research 36 25312268
2005 Heat shock-mediated regulation of MKP-1. American journal of physiology. Cell physiology 36 15958526
2019 Addiction to DUSP1 protects JAK2V617F-driven polycythemia vera progenitors against inflammatory stress and DNA damage, allowing chronic proliferation. Oncogene 34 30967632
2009 Role of MKP-1 in osteoclasts and bone homeostasis. The American journal of pathology 34 19762714
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
2015 Association Between MKP-1, BDNF, and Gonadal Hormones with Depression on Perimenopausal Women. Journal of women's health (2002) 30 26176177
2014 Specific calcineurin targeting in macrophages confers resistance to inflammation via MKP-1 and p38. The EMBO journal 30 24596247
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 29 30844440
2023 p38 MAPK and MKP-1 control the glycolytic program via the bifunctional glycolysis regulator PFKFB3 during sepsis. The Journal of biological chemistry 28 36803959
2020 Lnc-FAM84B-4 acts as an oncogenic lncRNA by interacting with protein hnRNPK to restrain MAPK phosphatases-DUSP1 expression. Cancer letters 28 32866608
2015 Mitogen-Dependent Regulation of DUSP1 Governs ERK and p38 Signaling During Early 3T3-L1 Adipocyte Differentiation. Journal of cellular physiology 28 26566083
2012 MKP-1: a critical phosphatase in the biology of macrophages controlling the switch between proliferation and activation. European journal of immunology 28 22865045
2008 Cadmium specifically induces MKP-1 expression via the glutathione depletion-mediated p38 MAPK activation in C6 glioma cells. Neuroscience letters 28 18573614
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
2007 Dual specificity phosphatase 1/CL100 is a direct transcriptional target of E2F-1 in the apoptotic response to oxidative stress. Cancer research 27 17638884
2004 Inhibition of MKP-1 expression potentiates JNK related apoptosis in renal cancer cells. The Journal of urology 27 15247770
2023 DUSP1 interacts with and dephosphorylates VCP to improve mitochondrial quality control against endotoxemia-induced myocardial dysfunction. Cellular and molecular life sciences : CMLS 26 37464072
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
2014 Isorhapontigenin (ISO) inhibited cell transformation by inducing G0/G1 phase arrest via increasing MKP-1 mRNA Stability. Oncotarget 25 24797581
2024 Down-regulation of MKP-1 in hippocampus protects against stress-induced depression-like behaviors and neuroinflammation. Translational psychiatry 24 38424085
2020 miR-378a-3p inhibits ischemia/reperfusion-induced apoptosis in H9C2 cardiomyocytes by targeting TRIM55 via the DUSP1-JNK1/2 signaling pathway. Aging 24 32463795
2017 MKP-1 suppresses PARP-1 degradation to mediate cisplatin resistance. Oncogene 24 28650468
2005 Heat shock triggers MAPK activation and MKP-1 induction in Leydig testicular cells. Biochemical and biophysical research communications 24 15629424
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) 23 38962952
2017 DUSP1 is involved in the progression of small cell carcinoma of the prostate. Saudi journal of biological sciences 23 30108432
2012 Knockout of Mkp-1 exacerbates colitis in Il-10-deficient mice. American journal of physiology. Gastrointestinal and liver physiology 23 22461024
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
2012 MKP-1 coordinates ordered macrophage-phenotype transitions essential for stem cell-dependent tissue repair. Cell cycle (Georgetown, Tex.) 22 22361726
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
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
2016 RIG-I inhibits the MAPK-dependent proliferation of BRAF mutant melanoma cells via MKP-1. Cellular signalling 20 26829212
2014 MKP-1 is a target of miR-210 and mediate the negative regulation of miR-210 inhibitor on hypoxic hPASMC proliferation. Cell biology international 20 25044272
2020 MiR-101 promotes pain hypersensitivity in rats with chronic constriction injury via the MKP-1 mediated MAPK pathway. Journal of cellular and molecular medicine 19 32656992
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 19 30388313
2018 Puerarin promotes DUSP1 expression by regulating miR‑133a‑3p in breast cancer. Molecular medicine reports 19 30483784
2017 Induction of Mkp-1 and Nuclear Translocation of Nrf2 by Limonoids from Khaya grandifoliola C.DC Protect L-02 Hepatocytes against Acetaminophen-Induced Hepatotoxicity. Frontiers in pharmacology 19 28974930
2022 CircHIPK3 alleviates inflammatory response and neuronal apoptosis via regulating miR-382-5p/DUSP1 axis in spinal cord injury. Transplant immunology 18 35500847
2022 Edaravone Dexborneol Alleviates Cerebral Ischemic Injury via MKP-1-Mediated Inhibition of MAPKs and Activation of Nrf2. BioMed research international 18 36110124
2020 Angiotensin (1-7) Inhibits Ang II-mediated ERK1/2 Activation by Stimulating MKP-1 Activation in Vascular Smooth Muscle Cells. International journal of molecular and cellular medicine 18 32832484
2018 Dysregulation of Lipid Metabolism in Mkp-1 Deficient Mice during Gram-Negative Sepsis. International journal of molecular sciences 18 30563203
2016 Corticosteroid-Induced MKP-1 Represses Pro-Inflammatory Cytokine Secretion by Enhancing Activity of Tristetraprolin (TTP) in ASM Cells. Journal of cellular physiology 18 26825339
2013 Involvement of the cellular phosphatase DUSP1 in vaccinia virus infection. PLoS pathogens 18 24244156
2010 Exercise training upregulates macrophage MKP-1 and affects immune responses in mice. Medicine and science in sports and exercise 18 20404768
2022 RGD1564534 represses NLRP3 inflammasome activity in cerebral injury following ischemia-reperfusion by impairing miR-101a-3p-mediated Dusp1 inhibition. Experimental neurology 17 36336032
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 16 40041918
2022 A Novel L-Phenylalanine Dipeptide Inhibits the Growth and Metastasis of Prostate Cancer Cells via Targeting DUSP1 and TNFSF9. International journal of molecular sciences 16 36142828
2018 miR-424 protects PC-12 cells from OGD-induced injury by negatively regulating MKP-1. European review for medical and pharmacological sciences 16 29565504
2009 Rosiglitazone reduces cell invasiveness by inducing MKP-1 in human U87MG glioma cells. Cancer letters 16 19168281
2021 Tim-3 suppresses autoimmune hepatitis via the p38/MKP-1 pathway in Th17 cells. FEBS open bio 15 33728805