Affinage

DUSP16

Dual specificity protein phosphatase 16 · UniProt Q9BY84

Length
665 aa
Mass
73.1 kDa
Annotated
2026-06-09
40 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DUSP16 (MKP-7) is a cytoplasmic dual-specificity MAPK phosphatase that functions as a context-dependent negative-feedback regulator of stress-activated MAPK signaling, binding and inactivating JNK/SAPK and p38α/β but not ERK or p38γ/δ (PMID:11359773). It carries a C-terminal NES/NLS and shuttles between nucleus and cytoplasm in a CRM1-dependent manner, predominantly resting in the cytoplasm where it sequesters phospho-MAPKs and so restricts their nuclear access (PMID:11489891, PMID:36272649); an allosteric tyrosine (Y271) is required both for catalytic activity and for efficient MAPK binding and cytoplasmic sequestration (PMID:36272649). Catalytic specificity extends to additional substrates including JNK3 presented on the β-arrestin 2 scaffold during receptor signaling (PMID:15888437). DUSP16 stability and abundance are tightly controlled: ERK phosphorylates Ser-446 to extend its half-life, while polyubiquitination drives proteasomal turnover (PMID:15689616), with FBXL18 acting as an E3 ligase that promotes its degradation (PMID:40382593). Its activity is further modulated post-translationally—inactivated by eNOS-dependent S-nitrosylation (PMID:19307591) and activated by Mycobacterium tuberculosis Eis-mediated acetylation at Lys55, a bacterial strategy to suppress JNK-dependent autophagy and ROS in macrophages (PMID:22547814). Through dampening of JNK and p38, DUSP16 governs diverse processes: it restrains TLR-induced macrophage cytokine output and is required for perinatal viability (PMID:24311790), balances neural progenitor proliferation versus differentiation during neurogenesis (PMID:29170629, PMID:39434411), protects cells from JNK/p38→BAX-driven mitochondrial apoptosis to confer chemoresistance (PMID:33863904), and shapes Th1/Th2 differentiation under epigenetic control (PMID:21613215). Its transcription is regulated by NR4A1, KLF6, ELK1, STAT3, and PPAR-driven mRNA stabilization, and it is epigenetically silenced by CpG methylation in Burkitt's lymphoma, removing a brake on JNK activity (PMID:34088892, PMID:42258131, PMID:39434411, PMID:38583797, PMID:23639976, PMID:20551953).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2001 High

    Established the foundational identity of DUSP16 as a dual-specificity phosphatase with defined MAPK substrate selectivity and cytoplasmic localization, distinguishing it from related family members.

    Evidence Cloning, co-IP, in vitro phosphatase assays and immunofluorescence in cultured cells

    PMID:11359773 PMID:11489891

    Open questions at the time
    • Endogenous physiological substrates beyond overexpression not yet tested
    • Regulation of shuttling by signaling inputs not defined
  2. 2005 High

    Showed that DUSP16 abundance is dynamically set by ERK phosphorylation at Ser-446 and proteasomal degradation, defining a stability-based control layer on phosphatase output.

    Evidence Metabolic pulse-labeling, proteasome inhibition, ubiquitination assay and phospho-mutant analysis

    PMID:15689616

    Open questions at the time
    • E3 ligase responsible not identified at the time
    • Physiological signals driving ERK-dependent stabilization unclear
  3. 2005 High

    Defined a scaffold-targeting mechanism whereby DUSP16 dephosphorylates JNK3 docked on β-arrestin 2, linking phosphatase action to receptor-localized signaling pools.

    Evidence Reciprocal co-IP with deletion mapping, receptor stimulation and endosomal localization imaging

    PMID:15888437

    Open questions at the time
    • Generalizability to other GPCRs untested
    • Functional output of dynamic association/dissociation not quantified
  4. 2009 High

    Identified S-nitrosylation as a reversible inactivating modification that couples eNOS/NO signaling to JNK3 release, showing DUSP16 activity is gated by redox post-translational modification.

    Evidence eNOS/MKP7 siRNA, S-nitrosylation assay and endothelial migration readout

    PMID:19307591

    Open questions at the time
    • Modified cysteine residue not mapped
    • Reversibility kinetics in vivo unknown
  5. 2012 High

    Revealed that a bacterial acetyltransferase (Mtb Eis) activates DUSP16 by Lys55 acetylation to suppress host JNK-dependent autophagy, defining a host-pathogen subversion mechanism with structural basis.

    Evidence In vitro acetyltransferase assay, crystal structures, mutagenesis and macrophage functional assays

    PMID:22547814

    Open questions at the time
    • Endogenous host acetyltransferase, if any, unidentified
    • Whether Lys55 acetylation occurs in non-infectious contexts unknown
  6. 2022 High

    Mapped Tyr271 as an allosteric residue coupling catalytic activity, MAPK binding, and cytoplasmic sequestration, mechanistically unifying enzymatic and sequestering functions.

    Evidence Site-directed mutagenesis with dephosphorylation, co-IP binding and localization assays

    PMID:36272649

    Open questions at the time
    • Structural mechanism of allostery not solved
    • Upstream regulators of Y271 status unknown
  7. 2013 High

    Genetic loss-of-function in mice established DUSP16 as essential for perinatal viability and as a brake on both p38 and JNK in TLR-driven macrophage cytokine programs.

    Evidence Gene-trap knockout mouse, MAPK phospho-assays, cytokine ELISA and JNK epistasis by siRNA/inhibitor

    PMID:24311790

    Open questions at the time
    • Cause of perinatal lethality not defined in this study
    • Tissue-specific contributions not dissected
  8. 2017 High

    Defined an in vivo developmental role: DUSP16 balances neural progenitor proliferation and cell-cycle exit, with loss causing brain overgrowth and obstructive hydrocephalus.

    Evidence Dusp16 knockout mouse, histology and BrdU/Ki67 cell-cycle analysis

    PMID:29170629

    Open questions at the time
    • Specific MAPK substrate driving progenitor expansion not pinpointed
    • Relationship to perinatal lethality phenotype unresolved
  9. 2021 High

    Established DUSP16 as a chemoresistance factor that blocks JNK/p38→BAX mitochondrial apoptosis across multiple cancer types, providing a therapeutic rationale for its inhibition.

    Evidence Gain/loss-of-function, phospho-MAPK and BAX mitochondrial localization assays in multiple cancer lines

    PMID:33863904

    Open questions at the time
    • In vivo tumor validation limited
    • Selectivity of BAX regulation between JNK and p38 not resolved
  10. 2026 Medium

    Defined a broad transcriptional and post-transcriptional regulatory network (NR4A1, KLF6, ELK1, STAT3, PPARδ/γ, miRNAs, CpG methylation) that tunes DUSP16 levels across tissues and disease states.

    Evidence Promoter/ChIP analyses, knockouts, miRNA manipulation and methylation profiling across immune, vascular, bone, neural and cancer contexts

    PMID:19826043 PMID:20551953 PMID:21613215 PMID:23639976 PMID:27771463 PMID:29880481 PMID:34088892 PMID:38583797 PMID:39434411 PMID:42258131

    Open questions at the time
    • Relative dominance of each regulator in specific tissues unclear
    • Cross-talk between transcriptional and stability control not integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DUSP16's enzymatic dephosphorylation versus non-catalytic cytoplasmic sequestration is selected in a given cellular context, and whether substrates beyond JNK/p38 (e.g. ERK anchoring, PRAS40/mTOR) are physiologically significant, remains unresolved.
  • No structural model integrating Y271 allostery with substrate choice
  • Non-MAPK substrate claims rest on single-lab overexpression studies
  • Mechanism balancing degradation vs ERK-stabilization in vivo undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 3 GO:0140313 molecular sequestering activity 3 GO:0016787 hydrolase activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-1266738 Developmental Biology 2 R-HSA-5357801 Programmed Cell Death 2
Partners
ARRB2FBXL18MAPK1MAPK14MAPK8TAK1

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 MKP-7 (DUSP16) was cloned and characterized as a novel dual-specificity phosphatase that binds to and inactivates JNK/SAPK and p38α and p38β MAPKs, but not ERK or p38γ/δ. MKP-7 is predominantly localized in the cytoplasm when expressed in cultured cells, distinguishing it from the related hVH5 which localizes to both nucleus and cytoplasm. Co-immunoprecipitation, overexpression in cultured cells, subcellular localization by immunofluorescence, in vitro phosphatase assay The Journal of Biological Chemistry High 11359773
2001 MKP-7 (DUSP16) contains a C-terminal stretch with both a nuclear export signal (NES) and nuclear localization signal (NLS). It shuttles between nucleus and cytoplasm in a leptomycin B-sensitive (CRM1-dependent) manner, and is predominantly cytoplasmic. A phosphatase-dead dominant-negative mutant selectively blocks JNK dephosphorylation, establishing MKP-7 as a JNK-specific phosphatase in vivo. Co-immunoprecipitation and histological analysis showed MKP-7 sequesters MAPKs in the cytoplasm. Mutagenesis of NES and NLS, leptomycin B treatment, co-immunoprecipitation, subcellular fractionation/immunofluorescence, overexpression assay in COS-7 cells The Journal of Biological Chemistry High 11489891
2005 MKP-7 stability is regulated by phosphorylation at Ser-446 by activated ERK. Phosphorylated MKP-7 (or phospho-mimic mutant) has a longer half-life than unphosphorylated MKP-7. MKP-7 is polyubiquitinated and degraded by the proteasome; deletion of the C-terminal stretch or proteasome inhibitors prolong its half-life. 35S-pulse labeling, proteasome inhibitor treatment, co-expression with ubiquitin, phospho-mimic/phospho-null mutagenesis at Ser-446 The Journal of Biological Chemistry High 15689616
2005 MKP7 (DUSP16) binds to the JNK3 scaffold protein β-arrestin 2 via MKP7 amino acids 394–443 (the same region that interacts with JIP-1). MKP7 dephosphorylates JNK3 bound to β-arrestin 2 following ASK1 overexpression or AT1aR stimulation. Initial AT1aR stimulation causes rapid MKP7 dissociation from β-arrestin 2 (within 5 min), followed by reassociation on endocytic vesicles 30–60 min later. Co-immunoprecipitation, deletion mutagenesis, receptor stimulation assay, immunofluorescence on endocytic vesicles The Journal of Biological Chemistry High 15888437
2009 SDF-1α signaling activates eNOS, which produces NO that S-nitrosylates MKP7 (DUSP16), rendering the phosphatase inactive. This allows JNK3 activation, which is required for SDF-1α-induced endothelial cell migration. siRNA knockdown of eNOS and MKP7, S-nitrosylation assay, JNK3 phosphorylation measurement, endothelial migration assay Proceedings of the National Academy of Sciences of the United States of America High 19307591
2010 MKP-7 (DUSP16) physically interacts with ERK but does not efficiently dephosphorylate it. Instead, MKP-7 acts as a cytoplasmic scaffold/anchor for phosphorylated ERK, blocking its nuclear translocation and thereby suppressing ERK-dependent gene transcription. This effect is observed with both wild-type and phosphatase-dead MKP-7. Immunofluorescence co-localization, reporter gene assay, time-course phospho-ERK analysis, overexpression of phosphatase-dead mutant Biochemical and biophysical research communications Medium 20122898
2012 Mycobacterium tuberculosis Eis protein acetylates Lys55 of DUSP16/MKP-7 (an Nε-acetyltransferase activity), which activates DUSP16 to dephosphorylate JNK, thereby suppressing JNK-dependent autophagy, phagosome maturation, and ROS generation in macrophages. Crystal structures of Mtb Eis and Msm Eis were solved and used to explain the substrate preference; the narrow active-site channel of Mtb Eis enables sequence-specific recognition of DUSP16/MKP-7. Biochemical acetyltransferase assay, site-specific mutagenesis, crystal structure determination, JNK phosphorylation assay, LPS stimulation of macrophages Proceedings of the National Academy of Sciences of the United States of America High 22547814
2003 Overexpression of DUSP16 in BCR-ABL-transformed Rat-1 fibroblasts reduces their transforming capacity in vitro and in vivo by downregulating BCR-ABL-induced JNK activation. Overexpression in Ba/F3 cells increased anti-apoptotic activity. Overexpression in transformed fibroblasts, soft agar/in vivo transformation assay, JNK phosphorylation western blot Oncogene Medium 14586399
2009 miR-24 directly downregulates DUSP16/MKP-7 protein expression, leading to enhanced phosphorylation of JNK and p38 kinases and stimulating myeloid cell growth and blocking differentiation. This is downstream of altered Runx1 subnuclear targeting. miR-24 overexpression, western blot for MKP-7 protein, JNK/p38 phosphorylation assay, myeloid differentiation assay Cancer Research Medium 19826043
2011 Flagellin induces MKP-7 expression (peaking at 2 h) via TLR5, leading to suppression of phosphorylated JNK. Constitutive MKP-7 expression in cultured cells protects against radiation-induced apoptosis, establishing MKP-7 as a cytoprotective negative feedback regulator of the JNK pathway. Adenoviral MKP-7 expression, tlr5-/- knockout mice, flow cytometry apoptosis assay, immunoblot for phospho-JNK, gene expression profiling Gut Medium 21199832
2011 DUSP16 (MKP-7) is selectively expressed in Th2 cells and its expression is regulated by histone H3/H4 acetylation at the dusp16 promoter (assessed by ChIP) under Th2 conditions. Adenoviral transduction of DUSP16 increases IL-4 and GATA-3 mRNA in Th2 cells and decreases IFNγ and T-bet in Th1 differentiation; dominant-negative DUSP16 has the reverse effects. In vivo, T cell-specific DUSP16 transgenic mice show altered antigen-specific IgG subclass ratios consistent with reduced Th1 responses. ChIP, adenoviral transduction, RT-PCR, in vitro Th1/Th2 differentiation, T cell-specific transgenic mouse immunization The Journal of Biological Chemistry High 21613215
2013 After cerebral ischemia/reperfusion in rat hippocampus, MKP-7 is upregulated and its nuclear export (CRM1-dependent) is required for cytoplasmic JNK inactivation. siRNA knockdown of MKP-7 or inhibition of its nuclear export with leptomycin B enhanced JNK activity. This regulation of JNK by MKP-7 occurs independently of the PI3K/Akt pathway. siRNA knockdown in rat ischemia model, cycloheximide chase, leptomycin B treatment, subcellular fractionation, phospho-JNK western blot BMC Neuroscience Medium 23280045
2013 PPARδ activation stabilizes MKP-7 mRNA (post-transcriptional regulation), leading to suppression of JNK (but not p38 or ERK) signaling and reduced MMP-1 secretion in UVB-exposed human dermal fibroblasts. This was confirmed in vivo in hairless mice where PPARδ ligand restored MKP-7 levels and reduced JNK phosphorylation. siRNA knockdown of PPARδ, mRNA stability assay, phospho-JNK western blot, MMP-1 ELISA, in vivo mouse model The Journal of Investigative Dermatology Medium 23639976
2014 miR-17 promotes MKP7 transcription via ADCY5 repression, which translocates membrane-bound RGS2 into the nucleus to interact with HIF1α and the MKP7 promoter. Additionally, ADCY5 repression facilitates translocation of EGFR and MKP7 from the membrane into cytoplasmic and mitochondrial fractions. MKP7 inhibits cellular senescence by dephosphorylating PRAS40 at Thr246 and mTOR at Ser2248. miR-17 transgenic mice, siRNA knockdown, subcellular fractionation, phosphorylation analysis of PRAS40 and mTOR, promoter analysis Cell Death & Disease Medium 25077541
2015 DUSP16 ablation causes G1/S cell cycle arrest, reduced BrdU incorporation, and cellular senescence (evidenced by β-galactosidase activity and senescence-associated heterochromatic foci) through activation of p53 and Rb tumor suppressors. The phosphatase activity of DUSP16 is required to antagonize cellular senescence. shRNA knockdown, BrdU incorporation, β-galactosidase assay, phosphatase-dead mutant rescue, western blot for p53/Rb The FEBS Journal Medium 26381291
2013 Dusp16-deficient mice (gene trap) die perinatally. Dusp16-deficient fibroblasts show enhanced activation of both p38 and JNK MAPKs. Dusp16-deficient macrophages selectively overexpress a subset of TLR-induced genes including IL-12, and pharmacological inhibition or siRNA knockdown of JNK1/2 normalizes IL-12p40 secretion, placing Dusp16 upstream of JNK in macrophage TLR signaling. Gene trap knockout mouse, MAPK phosphorylation assay, ELISA for cytokines, siRNA knockdown of JNK1/2, pharmacological JNK inhibition The Journal of Biological Chemistry High 24311790
2017 Genetic inactivation of Dusp16 in mice causes fully penetrant congenital obstructive hydrocephalus and brain overgrowth due to a delayed cell cycle exit of neural progenitors (expansion of progenitor pool) leading to aqueduct obstruction. Dusp16 is required to balance neural progenitor proliferation and differentiation during neurogenesis. Dusp16-/- knockout mouse, histology, BrdU/Ki67 cell cycle analysis, immunofluorescence for neural progenitor markers Frontiers in Molecular Neuroscience High 29170629
2018 HIF-1 transcriptionally decreases DUSP16 expression in response to chemotherapy in triple-negative breast cancer, leading to p38 MAPK activation. Activated p38 stabilizes Nanog and Klf4 mRNA through increased inactivating phosphorylation of RNA-binding protein ZFP36L1, promoting breast cancer stem cell enrichment. HIF1 siRNA/inhibitor, DUSP16 knockdown/overexpression, p38 phosphorylation assay, RNA-binding protein phosphorylation, stem cell enrichment assays Cancer Research Medium 29880481
2020 DUSP16 directly interacts with TAK1 in human hepatocytes (identified by Co-IP). DUSP16 negatively regulates JNK, TAK1, and NF-κB signaling to suppress palmitate-induced lipid deposition and inflammatory responses in hepatocytes. In vivo, DUSP16 knockout in mice aggravates HFD-induced metabolic disorder and hepatic steatosis. Co-immunoprecipitation, DUSP16 knockdown/overexpression in primary hepatocytes, DUSP16 knockout mouse on HFD, JNK/TAK1/NF-κB phosphorylation assays Biochemical and Biophysical Research Communications Medium 31982140
2020 Photobiomodulation (PBM) activates ERK, which phosphorylates and stabilizes MKP7, resulting in inactivation of JNK3 (a brain-specific JNK isoform). MKP7-dependent suppression of JNK3 prevents AMPA receptor endocytosis and attenuates Aβ-induced synaptic dysfunction. Phospho-ERK and phospho-JNK3 western blotting, MKP7 knockdown/overexpression, AMPA receptor surface expression assay, APP/PS1 mouse model Aging Cell Medium 33336891
2021 DUSP16 inhibits JNK and p38 activation, thereby reducing BAX accumulation in mitochondria and blocking mitochondria-mediated apoptosis in response to chemotherapy. Knockdown of DUSP16 sensitizes cancer cells to chemotherapy-induced cell death. DUSP16 knockdown/overexpression, phospho-JNK and phospho-p38 western blot, BAX mitochondrial localization assay, apoptosis assays across multiple cancer cell lines Nature Communications High 33863904
2021 NR4A1 transcription factor directly binds two putative binding sites in the MKP7 promoter to enhance MKP7 transcription. NR4A1 knockout mice show reduced MKP7 expression in pancreatic β cells; overexpression of NR4A1 increases MKP7. Knockdown of MKP7 increases p-JNK levels in β cells under ER-stress or ROS conditions. NR4A1 knockout mouse, MIN6 cell overexpression/knockdown, promoter-reporter assay, ChIP-like binding site validation, phospho-JNK assay Cell Death Discovery Medium 34088892
2022 Tyrosine 271 (Y271) in MKP7 is a novel allosteric site required for both catalytic activity and MAPK binding. Mutation of Y271 inhibits MKP7 catalytic activity, reduces its binding efficiency to p38 MAPK and JNK1/2, and prevents dephosphorylation of these substrates in cells. MKP7 Y271 mutants also fail to sequester p38/JNK in the cytoplasm, leading to increased nuclear accumulation of these MAPKs. Site-directed mutagenesis (Y271 variants), in-cell dephosphorylation assay, Co-immunoprecipitation for MAPK binding, subcellular localization by immunofluorescence The Journal of Biological Chemistry High 36272649
2016 PPARγ activation by rosiglitazone upregulates MKP-7, a JNK-specific phosphatase, which inactivates JNK-1 to prevent JNK-1-mediated phosphorylation of SIRT1 at Ser-46 and subsequent proteasome-mediated SIRT1 degradation in LPS-activated macrophages. Gain-of-MKP-7 function mimics rosiglitazone's stabilization of SIRT1. MKP-7 overexpression/ablation, phospho-SIRT1 Ser-46 western blot, ubiquitination assay, proteasome inhibitor experiment Pharmacological Research Medium 27771463
2011 MKP-7 negatively regulates JNK, and its siRNA silencing leads to increased JNK phosphorylation, reduced IRF-1 protein levels and reduced IRF-1 binding to the VCAM-1 promoter (confirmed by ChIP), resulting in decreased VCAM-1 expression. This identifies a MKP-7→JNK→IRF-1→VCAM-1 signaling axis in endothelial cells. siRNA knockdown, phospho-JNK western blot, ChIP assay for IRF-1 promoter binding, VCAM-1 expression assay Cellular Signalling Medium 22182512
2010 DUSP16 CpG island methylation causes transcriptional silencing in Burkitt's lymphoma (BL) cell lines and primary BL, specifically blocking constitutive and inducible DUSP16 expression. This methylation abrogates a normal negative feedback loop limiting JNK activity; BL lines with DUSP16 methylation show increased JNK activation and increased sensitivity to JNK-activating agents. Bisulfite sequencing, methylation-specific PCR, RT-PCR/qPCR, phospho-JNK/ERK/p38 western blot British Journal of Cancer Medium 20551953
2024 ELK1 transcription factor promotes DUSP16 transcription in AD mouse models, leading to DUSP16 upregulation that impairs neural progenitor cell differentiation by suppressing JNK phosphorylation and downregulating SOX2 expression. Silencing DUSP16 in AD mice restores NPC differentiation and cognitive function. DUSP16 silencing in 3xTg and SAMP8 AD mice, promoter analysis for ELK1 binding, phospho-JNK and SOX2 western blot, behavioral testing Aging Cell Medium 39434411
2024 ILF3 promotes HMGB1 mRNA stability; ILF3 loss leads to HMGB1 mRNA degradation, which reduces STAT3 phosphorylation, thereby de-repressing DUSP16 transcription (STAT3 normally inhibits DUSP16). Increased DUSP16 then suppresses VSMC phenotype switching, proliferation, and migration. RIP-seq, transcriptome sequencing, Co-IP, siRNA knockdown, SMC-specific ILF3 KO mouse, STAT3 phosphorylation assay, DUSP16 mRNA/protein measurement Journal of Molecular and Cellular Cardiology Medium 38583797
2025 FBXL18 (an F-box protein) physically interacts with DUSP16 and promotes its ubiquitination and proteasomal degradation, thereby activating JNK/c-JUN signaling to facilitate endometrial carcinoma progression. Co-immunoprecipitation, ubiquitination assay, western blot, overexpression/knockdown rescue experiments Cancer Cell International Medium 40382593
2026 KLF6 transcription factor upregulates DUSP16 expression (identified by RNA sequencing and ChIP), thereby inhibiting MAPK signaling and suppressing osteoclast differentiation. KLF6 overexpression via AAV reduces OVX-induced bone loss in mice. RNA sequencing, ChIP analysis, KLF6 overexpression via AAV, in vivo OVX mouse model, osteoclast differentiation assay Science China. Life Sciences Medium 42258131

Source papers

Stage 0 corpus · 40 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Mycobacterium tuberculosis Eis protein initiates suppression of host immune responses by acetylation of DUSP16/MKP-7. Proceedings of the National Academy of Sciences of the United States of America 172 22547814
2001 A Novel MAPK phosphatase MKP-7 acts preferentially on JNK/SAPK and p38 alpha and beta MAPKs. The Journal of biological chemistry 137 11359773
2001 MKP-7, a novel mitogen-activated protein kinase phosphatase, functions as a shuttle protein. The Journal of biological chemistry 127 11489891
2009 Altered Runx1 subnuclear targeting enhances myeloid cell proliferation and blocks differentiation by activating a miR-24/MKP-7/MAPK network. Cancer research 102 19826043
2018 Reciprocal Regulation of DUSP9 and DUSP16 Expression by HIF1 Controls ERK and p38 MAP Kinase Activity and Mediates Chemotherapy-Induced Breast Cancer Stem Cell Enrichment. Cancer research 75 29880481
2009 SDF-1alpha stimulates JNK3 activity via eNOS-dependent nitrosylation of MKP7 to enhance endothelial migration. Proceedings of the National Academy of Sciences of the United States of America 68 19307591
2021 DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death. Nature communications 64 33863904
2005 Phosphorylation of Ser-446 determines stability of MKP-7. The Journal of biological chemistry 56 15689616
2011 Flagellin administration protects gut mucosal tissue from irradiation-induced apoptosis via MKP-7 activity. Gut 54 21199832
2014 miR-17 extends mouse lifespan by inhibiting senescence signaling mediated by MKP7. Cell death & disease 53 25077541
2005 Dynamic interaction between the dual specificity phosphatase MKP7 and the JNK3 scaffold protein beta-arrestin 2. The Journal of biological chemistry 52 15888437
2003 MAPK phosphatase DUSP16/MKP-7, a candidate tumor suppressor for chromosome region 12p12-13, reduces BCR-ABL-induced transformation. Oncogene 45 14586399
2013 PI3K/Akt-independent negative regulation of JNK signaling by MKP-7 after cerebral ischemia in rat hippocampus. BMC neuroscience 42 23280045
2020 Photobiomodulation suppresses JNK3 by activation of ERK/MKP7 to attenuate AMPA receptor endocytosis in Alzheimer's disease. Aging cell 35 33336891
2018 MicroRNA-27a-3p inhibits cell viability and migration through down-regulating DUSP16 in hepatocellular carcinoma. Journal of cellular biochemistry 34 29143999
2021 Exosomal transfer of miR-769-5p promotes osteosarcoma proliferation and metastasis by targeting DUSP16. Cancer cell international 30 34663350
2010 DUSP16 is an epigenetically regulated determinant of JNK signalling in Burkitt's lymphoma. British journal of cancer 29 20551953
2013 PPARδ inhibits UVB-induced secretion of MMP-1 through MKP-7-mediated suppression of JNK signaling. The Journal of investigative dermatology 28 23639976
2015 DUSP16 ablation arrests the cell cycle and induces cellular senescence. The FEBS journal 24 26381291
2013 Gene trap mice reveal an essential function of dual specificity phosphatase Dusp16/MKP-7 in perinatal survival and regulation of Toll-like receptor (TLR)-induced cytokine production. The Journal of biological chemistry 24 24311790
2011 Functional involvement of dual specificity phosphatase 16 (DUSP16), a c-Jun N-terminal kinase-specific phosphatase, in the regulation of T helper cell differentiation. The Journal of biological chemistry 23 21613215
2010 MKP-7, a JNK phosphatase, blocks ERK-dependent gene activation by anchoring phosphorylated ERK in the cytoplasm. Biochemical and biophysical research communications 18 20122898
2016 Upregulation of MKP-7 in response to rosiglitazone treatment ameliorates lipopolysaccharide-induced destabilization of SIRT1 by inactivating JNK. Pharmacological research 17 27771463
2022 circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury. Open medicine (Warsaw, Poland) 16 35291714
2021 NR4A1 enhances MKP7 expression to diminish JNK activation induced by ROS or ER-stress in pancreatic β cells for surviving. Cell death discovery 16 34088892
2020 Targeting DUSP16/TAK1 signaling alleviates hepatic dyslipidemia and inflammation in high fat diet (HFD)-challenged mice through suppressing JNK MAPK. Biochemical and biophysical research communications 16 31982140
2011 MKP-7, a negative regulator of JNK, regulates VCAM-1 expression through IRF-1. Cellular signalling 16 22182512
2017 Dusp16 Deficiency Causes Congenital Obstructive Hydrocephalus and Brain Overgrowth by Expansion of the Neural Progenitor Pool. Frontiers in molecular neuroscience 15 29170629
2023 Mettl3 induced miR-338-3p expression in dendritic cells promotes antigen-specific Th17 cell response via regulation of Dusp16. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 14 37878342
2021 CircRNA DUSP16 Knockdown Suppresses Colorectal Cancer Progression by Regulating the miR-432-5p/E2F6 Axis. Cancer management and research 14 34456589
2022 A novel site on dual-specificity phosphatase MKP7/DUSP16 is required for catalysis and MAPK binding. The Journal of biological chemistry 9 36272649
2014 Discovery of novel DUSP16 phosphatase inhibitors through virtual screening with homology modeled protein structure. Journal of biomolecular screening 9 25245988
2024 Deficiency of smooth muscle cell ILF3 alleviates intimal hyperplasia via HMGB1 mRNA degradation-mediated regulation of the STAT3/DUSP16 axis. Journal of molecular and cellular cardiology 7 38583797
2013 A docking study of enhanced intracellular survival protein from Mycobacterium tuberculosis with human DUSP16/MKP-7. Journal of synchrotron radiation 7 24121342
2024 Suppressing DUSP16 overexpression induced by ELK1 promotes neural progenitor cell differentiation in mouse models of Alzheimer's disease. Aging cell 3 39434411
2025 Regulatory roles of MKP7/DUSP16 in cancer. Medical oncology (Northwood, London, England) 1 41320681
2026 Zinc finger protein 383 suppresses tumor growth in NSCLC by upregulating DUSP16 expression to inactivate ERK signaling. Tissue & cell 0 42217294
2026 KLF6 regulates osteoclastogenesis through DUSP16 in OVX-induced bone loss. Science China. Life sciences 0 42258131
2025 FBXL18 promotes endometrial carcinoma progression via destabilizing DUSP16 and thus activating JNK signaling pathway. Cancer cell international 0 40382593
2025 SBEM confers paclitaxel resistance in breast cancer via DUSP16-mediated MAPK/AMPK pathway activation. Oncology letters 0 41181635

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