Affinage

DUSP7

Dual specificity protein phosphatase 7 · UniProt Q16829

Length
419 aa
Mass
45.0 kDa
Annotated
2026-06-09
16 papers in source corpus 9 papers cited in narrative 9 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DUSP7 (PYST2/MKP-X) is a predominantly cytosolic dual-specificity MAP kinase phosphatase that controls the amplitude of MAPK signaling by dephosphorylating and inactivating ERK2, toward which it shows substrate selectivity and to which it binds, with its catalytic activity allosterically stimulated upon MAP kinase binding (PMID:9788880). Through this ERK2-directed activity DUSP7 functions as a tunable counterweight to MEK during cell division: it binds active phospho-ERK2 during mitosis, and the balance between MEK-driven phosphorylation and DUSP7-driven dephosphorylation must be maintained for proper chromosome congression, as both catalytically active DUSP7 overexpression and DUSP7 depletion cause chromosome misalignment and prolonged mitosis (PMID:33865857). The same requirement extends to meiosis, where DUSP7 drives meiotic resumption in mouse oocytes by dephosphorylating and inactivating cPKC isoforms to sustain Cdk1/CycB activity above the threshold for nuclear envelope breakdown, and is again needed for correct chromosome alignment (PMID:27783954). Beyond ERK2, DUSP7 acts on additional substrates and partners in disease contexts: it suppresses the RAS/ERK pathway to restrain cancer cell invasion, migration, proliferation and tumor formation (PMID:34435746), dephosphorylates the adaptor PEA15 downstream of FOSL1 to promote drug resistance in breast cancer (PMID:34907034), and physically interacts with TAK1 in hepatocytes to negatively regulate inflammatory and lipogenic signaling in NAFLD (PMID:32311490). The DUSP7 locus encodes a catalytic isoform (PYST2-L) and a shorter isoform lacking the phosphatase domain (PYST2-S) (PMID:14603440).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1998 High

    Established DUSP7's core biochemical identity by defining it as a cytosolic dual-specificity phosphatase selective for ERK2 whose activity is switched on by MAP kinase binding.

    Evidence Subcellular fractionation, in vitro phosphatase assays, and in vivo substrate selectivity/binding in COS-1 cells

    PMID:9788880

    Open questions at the time
    • Structural basis of allosteric activation by ERK2 not resolved
    • Physiological signaling context for ERK2 inactivation not yet addressed
  2. 2004 Medium

    Refined the substrate specificity question by showing recombinant DUSP7 can also bind phospho-JNK, indicating ERK2 selectivity is not absolute.

    Evidence Overexpression with phospho-ERK1/2 Western blot and recombinant pull-down for phospho-JNK in HEK293 cells

    PMID:15081539

    Open questions at the time
    • JNK binding shown by pull-down without functional dephosphorylation in cells
    • Limited controls for binding specificity
  3. 2004 Medium

    Defined the gene architecture by identifying a catalytic isoform (PYST2-L) and a catalytically deficient short isoform (PYST2-S), raising the possibility of intramolecular regulation.

    Evidence Northern blot, RT-PCR, sequencing, Western blot, and domain analysis

    PMID:14603440

    Open questions at the time
    • Negative-regulatory role of PYST2-S inferred but not experimentally demonstrated
    • Relative abundance and tissue distribution of isoforms unknown
  4. 2005 Low

    Linked DUSP7 expression to cell-cycle phase and culture density, hinting at a cell-cycle regulatory function.

    Evidence Cell cycle synchronization and expression analysis in K562 cells plus crowding comparisons

    PMID:16386315

    Open questions at the time
    • Correlative expression only, no functional rescue or pathway placement
    • Mechanism connecting crowding to DUSP7 expression unknown
  5. 2016 High

    Demonstrated a physiological requirement for DUSP7 in meiosis, identifying cPKC isoforms as substrates whose dephosphorylation drives meiotic resumption and proper chromosome alignment.

    Evidence RNAi depletion in mouse oocytes with live imaging, Cdk1/CycB activity assays, and cPKC phosphorylation analysis

    PMID:27783954

    Open questions at the time
    • Direct enzyme-substrate dephosphorylation of cPKC not reconstituted in vitro
    • How cPKC links to the Cdk1/CycB threshold not fully mapped
  6. 2020 Medium

    Extended DUSP7's regulatory reach to inflammatory metabolism by showing it physically restrains TAK1 to limit NAFLD pathogenesis.

    Evidence Co-IP for TAK1 interaction and DUSP7 knockout mice under HFD with pathway and metabolic readouts

    PMID:32311490

    Open questions at the time
    • Whether DUSP7 dephosphorylates TAK1 or acts as a scaffold not distinguished
    • Single Co-IP without reciprocal biochemical validation of mechanism
  7. 2021 High

    Resolved the mitotic function of ERK2 dephosphorylation, establishing that a MEK/DUSP7 balance setting phospho-ERK2 levels governs chromosome congression.

    Evidence Co-IP of DUSP7 with ERK2 in mitosis, catalytic mutant overexpression, siRNA, chemical MEK/ERK inhibition, and chromosome alignment imaging

    PMID:33865857

    Open questions at the time
    • ERK2 substrates relevant to chromosome alignment not identified
    • Spatial regulation of DUSP7 activity at the spindle/kinetochore unknown
  8. 2021 Medium

    Positioned DUSP7 as a tumor suppressor in cervical cancer acting through inactivation of the RAS/ERK pathway.

    Evidence Overexpression and shRNA knockdown in SIHA cells with HRAS/p-ERK Western blots, in vitro phenotypic assays, and xenografts

    PMID:34435746

    Open questions at the time
    • Mechanism by which DUSP7 lowers HRAS not defined
    • No direct biochemical reconstitution of pathway suppression
  9. 2022 Medium

    Identified a FOSL1/DUSP7/PEA15 axis in which transcriptionally induced DUSP7 dephosphorylates PEA15 to promote chemoresistance, adding a new substrate and an upstream regulator.

    Evidence qRT-PCR, transcriptional/ChIP-type assays, phospho-PEA15 Western blot, and in vitro/in vivo drug resistance assays in breast cancer cells

    PMID:34907034

    Open questions at the time
    • Direct DUSP7-PEA15 dephosphorylation not reconstituted in vitro
    • How PEA15 dephosphorylation confers resistance mechanistically unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DUSP7's substrate choice (ERK2, cPKC, PEA15, TAK1) is partitioned across cell types, cell-cycle phases, and disease contexts, and the structural basis of its allosteric activation, remain unresolved.
  • No structural model of substrate engagement or activation
  • No unified framework reconciling ERK2-selective and multi-substrate activities
  • Determinants directing DUSP7 to distinct substrates in different tissues unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016787 hydrolase activity 2
Localization
GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 2
Partners
MAPK1PEA15TAK1

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 PYST2/DUSP7 protein is predominantly cytosolic when expressed in COS-1 cells. It shows substrate selectivity for ERK2 (p42 MAP kinase) both in vitro and in vivo, with much reduced activity toward stress-activated kinases JNK-1 and p38/RK. PYST2 binds p42 MAP kinase in vivo, and both MAP and SAP kinases can cause catalytic activation of PYST2 phosphatase activity in vitro. Subcellular fractionation/localization in COS-1 cells, in vitro phosphatase assays, in vivo substrate selectivity assays, in vivo co-binding experiments Journal of cell science High 9788880
2004 Overexpression of Pyst2-L in HEK293 cells reduced basal phospho-ERK1/2 levels. Pull-down experiments showed that recombinant Pyst2-L binds not only phospho-ERK1/2 but also phospho-JNK, indicating the phosphatase is not exclusively selective for ERK2. Overexpression in HEK293 cells with Western blot for phospho-ERK1/2; pull-down assay with recombinant Pyst2-L for phospho-JNK Immunology letters Medium 15081539
2004 The PYST2 locus encodes two alternatively transcribed and translated isoforms: PYST2-L (containing the phosphatase catalytic domain, PCD) and PYST2-S (lacking any known PCD). Both transcripts are translated into protein. PYST2-S may act as a negative regulator of PYST2-L. Northern blot, RT-PCR, sequencing, Western blot, bioinformatic domain analysis Genes, chromosomes & cancer Medium 14603440
2005 Pyst2-L expression is reduced in G2-phase-synchronized human K562 cells, consistent with homologous genes (yeast Yvh1p and Xenopus X17c) that regulate cell cycle. Cells in highly crowded cultures express high levels of Pyst2-L phosphatase, implicating it in crowding-induced signaling. Cell cycle synchronization with alpha-factor, Northern blot/expression analysis in synchronized K562 cells; comparative genomic analysis; expression measurement in crowded vs. non-crowded cultures Immunology letters Low 16386315
2016 DUSP7 is required for meiotic resumption in mouse oocytes. DUSP7-depleted oocytes fail to resume meiosis or do so with significant delay due to Cdk1/CycB activity dropping below the critical threshold for nuclear envelope breakdown. DUSP7 drives meiotic resumption by dephosphorylating and inactivating cPKC isoforms. Additionally, DUSP7 is required for proper chromosome alignment; DUSP7-depleted oocytes entering meiosis show severe chromosome alignment defects and premature anaphase progression. RNAi-mediated depletion in mouse oocytes, live cell imaging, Cdk1/CycB activity assays, cPKC phosphorylation analysis Cell reports High 27783954
2021 During mitosis, DUSP7 binds ERK2 and regulates the abundance of active phospho-ERK2 through its phosphatase activity. Overexpression of catalytically active DUSP7 (but not catalytically inactive mutants) decreases phospho-ERK2 levels and causes mitotic chromosome misalignment. Knockdown of DUSP7 also leads to defective chromosome congression and prolonged mitosis. Proper chromosome alignment requires MEK-mediated phosphorylation and DUSP7-mediated dephosphorylation to maintain appropriate levels of active phospho-ERK2. Co-immunoprecipitation of DUSP7 with ERK2 during mitosis, catalytic mutant overexpression, siRNA knockdown, immunofluorescence for chromosome alignment, phospho-ERK2 Western blot, chemical inhibition of ERK2 and MEK The Journal of biological chemistry High 33865857
2021 DUSP7 overexpression in cervical cancer SIHA cells decreases HRAS and phospho-ERK1/2 levels, suppresses invasion, migration, proliferation in vitro, and tumor formation in vivo, indicating DUSP7 inhibits cancer progression by inactivating the RAS/ERK pathway. DUSP7 overexpression and shRNA knockdown in SIHA cells, Western blot for HRAS and p-ERK1/2, in vitro invasion/migration/proliferation assays, in vivo xenograft tumor formation Journal of cellular and molecular medicine Medium 34435746
2022 FOSL1 transcription factor positively regulates DUSP7 transcription in doxorubicin-resistant breast cancer cells. DUSP7 in turn mediates dephosphorylation of PEA15 (proliferation and apoptosis adaptor protein 15), promoting drug resistance through this FOSL1/DUSP7/PEA15 pathway. qRT-PCR for FOSL1 and DUSP7, transcriptional reporter/ChIP-type assays, Western blot for phospho-PEA15, in vitro and in vivo drug resistance assays Molecular cancer research : MCR Medium 34907034
2020 DUSP7 physically interacts with TAK1 (TGF-β-activated kinase 1) in hepatocytes. DUSP7 knockout in mice promotes TAK1 activation, leading to increased lipid deposition, inflammatory response (via NF-κB and MAPK pathways), and ROS production in HFD-fed conditions. DUSP7 thus acts as a negative regulator of TAK1-driven NAFLD pathogenesis. Co-immunoprecipitation (physical interaction with TAK1), DUSP7 knockout mouse model, HFD-feeding experiments, Western blot for phospho-TAK1 and downstream pathway components, metabolic phenotyping Free radical biology & medicine Medium 32311490

Source papers

Stage 0 corpus · 16 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Isolation of the human genes encoding the pyst1 and Pyst2 phosphatases: characterisation of Pyst2 as a cytosolic dual-specificity MAP kinase phosphatase and its catalytic activation by both MAP and SAP kinases. Journal of cell science 110 9788880
2017 Long non-coding RNA MIAT promotes breast cancer progression and functions as ceRNA to regulate DUSP7 expression by sponging miR-155-5p. Oncotarget 105 29100300
2020 Circ-ABCB10 Contributes to Paclitaxel Resistance in Breast Cancer Through Let-7a-5p/DUSP7 Axis. Cancer management and research 81 32273769
2008 Expression of ERK signaling inhibitors Dusp6, Dusp7, and Dusp9 during mouse ear development. Developmental dynamics : an official publication of the American Association of Anatomists 33 18058922
2003 Overexpression of the dual-specificity MAPK phosphatase PYST2 in acute leukemia. Cancer letters 27 12969791
2003 Dual-specificity phosphatase Pyst2-L is constitutively highly expressed in myeloid leukemia and other malignant cells. Oncogene 27 14576828
2020 Targeting DUSP7 signaling alleviates hepatic steatosis, inflammation and oxidative stress in high fat diet (HFD)-fed mice via suppression of TAK1. Free radical biology & medicine 26 32311490
1997 Chromosomal localization of three human dual specificity phosphatase genes (DUSP4, DUSP6, and DUSP7). Genomics 25 9205128
2022 Transcription Factor FOSL1 Enhances Drug Resistance of Breast Cancer through DUSP7-Mediated Dephosphorylation of PEA15. Molecular cancer research : MCR 23 34907034
2016 The Phosphatase Dusp7 Drives Meiotic Resumption and Chromosome Alignment in Mouse Oocytes. Cell reports 18 27783954
2021 DUSP7 regulates the activity of ERK2 to promote proper chromosome alignment during cell division. The Journal of biological chemistry 12 33865857
2021 DUSP7 inhibits cervical cancer progression by inactivating the RAS pathway. Journal of cellular and molecular medicine 10 34435746
2017 mRNA profiling identifies low levels of phosphatases dual‐specific phosphatase‐7 (DUSP7) and cell division cycle‐25B (CDC25B) in patients with early arthritis. Clinical and experimental immunology 10 28253537
2004 Does the dual-specificity MAPK phosphatase Pyst2-L lead a monogamous relationship with the Erk2 protein? Immunology letters 10 15081539
2004 Characterization of the dual-specificity phosphatase PYST2 and its transcripts. Genes, chromosomes & cancer 3 14603440
2005 The Pyst2-L phosphatase is involved in cell-crowding. Immunology letters 0 16386315

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